VCP

Summary

Gene Symbol: VCP
Description: valosin containing protein
Alias: ALS14, CDC48, CMT2Y, HEL-220, HEL-S-70, IBMPFD, IBMPFD1, TERA, p97, transitional endoplasmic reticulum ATPase, 15S Mg(2+)-ATPase p97 subunit, TER ATPase, epididymis luminal protein 220, epididymis secretory protein Li 70, yeast Cdc48p homolog
Species: human

Top Publications

  1. pmc Tyrosine phosphorylation of p97 regulates transitional endoplasmic reticulum assembly in vitro
    C Lavoie
    Department of Anatomy and Cell Biology, McGill University, Montreal, QC, H3A 2B2, Canada
    Proc Natl Acad Sci U S A 97:13637-42. 2000
  2. ncbi Ataxin-3 binds VCP/p97 and regulates retrotranslocation of ERAD substrates
    Xiaoyan Zhong
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6084, USA
    Hum Mol Genet 15:2409-20. 2006
  3. pmc Gp78 cooperates with RMA1 in endoplasmic reticulum-associated degradation of CFTRDeltaF508
    Daisuke Morito
    Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8397, Japan
    Mol Biol Cell 19:1328-36. 2008
  4. ncbi Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein
    Giles D J Watts
    Division of Genetics, Children s Hospital Boston, 300 Longwood Avenue, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Genet 36:377-81. 2004
  5. doi Recent advances in p97/VCP/Cdc48 cellular functions
    Kunitoshi Yamanaka
    Department of Molecular Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, 2 2 1 Honjo, Kumamoto 860 0811, Japan
    Biochim Biophys Acta 1823:130-7. 2012
  6. pmc Derlin-1 is a rhomboid pseudoprotease required for the dislocation of mutant α-1 antitrypsin from the endoplasmic reticulum
    Ethan J Greenblatt
    Biophysics Program, Stanford University, Stanford, California, USA
    Nat Struct Mol Biol 18:1147-52. 2011
  7. pmc Critical role of VCP/p97 in the pathogenesis and progression of non-small cell lung carcinoma
    Christopher W Valle
    Department of Pediatric Respiratory Sciences, The Johns Hopkins School of Medicine, Baltimore, Maryland, USA
    PLoS ONE 6:e29073. 2011
  8. pmc The role of the N-domain in the ATPase activity of the mammalian AAA ATPase p97/VCP
    Hajime Niwa
    Centre for Structural Biology, Division of Molecular Biosciences, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, United Kingdom
    J Biol Chem 287:8561-70. 2012
  9. ncbi ATPase activity of p97/valosin-containing protein is regulated by oxidative modification of the evolutionally conserved cysteine 522 residue in Walker A motif
    Masakatsu Noguchi
    Laboratory of Functional Biology, Kyoto University Graduate School of Biostudies and Solution Oriented Research for Science and Technology JST, Kyoto 606 8501, Japan
    J Biol Chem 280:41332-41. 2005
  10. ncbi Novel VCP mutations in inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia
    G D J Watts
    Division of Genetics, Children s Hospital Boston, Harvard Medical School, Boston, MA, USA
    Clin Genet 72:420-6. 2007

Research Grants

  1. Conrad C Weihl; Fiscal Year: 2016
  2. Mariusz Karbowski; Fiscal Year: 2015
  3. James A Olzmann; Fiscal Year: 2015
  4. Defining the role of ubiquitination in the regulation of lipid droplet function
    James A Olzmann; Fiscal Year: 2013
  5. High-fat diet rescues lethality of homozygous knock-in R155H VCP myopathic mice
    VIRGINIA EUNICE KIMONIS; Fiscal Year: 2013
  6. Translational Studies in VCP Inclusion Body Myopathy with Paget Disease of Bone
    Virginia Kimonis; Fiscal Year: 2009
  7. Changcheng Song; Fiscal Year: 2014
  8. Cellular Mechanisms of Aggregation of Abnormal Proteins
    Michael Y Sherman; Fiscal Year: 2012
  9. The role of p97 in protein degradation during aging and disease
    EUGENE DROKHLYANSKY; Fiscal Year: 2013
  10. Ubiquitin and Cell Cycle Regulation of Golgi Membrane Dynamics
    Yanzhuang Wang; Fiscal Year: 2013

Detail Information

Publications241 found, 100 shown here

  1. pmc Tyrosine phosphorylation of p97 regulates transitional endoplasmic reticulum assembly in vitro
    C Lavoie
    Department of Anatomy and Cell Biology, McGill University, Montreal, QC, H3A 2B2, Canada
    Proc Natl Acad Sci U S A 97:13637-42. 2000
    The ATPase associated with different cellular activities family member p97, associated p47, and the t-SNARE syntaxin 5 are necessary for the cell-free reconstitution of transitional endoplasmic reticulum (tER) from starting low-density ..
  2. ncbi Ataxin-3 binds VCP/p97 and regulates retrotranslocation of ERAD substrates
    Xiaoyan Zhong
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6084, USA
    Hum Mol Genet 15:2409-20. 2006
    ..AT3 binds VCP/p97, a key protein responsible for extracting ERAD substrates from the ER; binding is modulated by the size of the ..
  3. pmc Gp78 cooperates with RMA1 in endoplasmic reticulum-associated degradation of CFTRDeltaF508
    Daisuke Morito
    Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8397, Japan
    Mol Biol Cell 19:1328-36. 2008
    ..Our data demonstrates that gp78 cooperates with RMA1 with E4-like activity in the ERAD of CFTRDeltaF508...
  4. ncbi Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein
    Giles D J Watts
    Division of Genetics, Children s Hospital Boston, 300 Longwood Avenue, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Genet 36:377-81. 2004
    Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia (IBMPFD) is a dominant progressive disorder that maps to chromosome 9p21.1-p12...
  5. doi Recent advances in p97/VCP/Cdc48 cellular functions
    Kunitoshi Yamanaka
    Department of Molecular Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, 2 2 1 Honjo, Kumamoto 860 0811, Japan
    Biochim Biophys Acta 1823:130-7. 2012
    ..a causative factor for inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia (IBMPFD) and more recently as a causative factor for amyotrophic lateral sclerosis (ALS)...
  6. pmc Derlin-1 is a rhomboid pseudoprotease required for the dislocation of mutant α-1 antitrypsin from the endoplasmic reticulum
    Ethan J Greenblatt
    Biophysics Program, Stanford University, Stanford, California, USA
    Nat Struct Mol Biol 18:1147-52. 2011
    ..degradation (ERAD) substrates must be dislocated across the ER membrane through a process driven by the AAA ATPase p97/VCP. Derlins recruit p97/VCP and have been proposed to be part of the dislocation machinery...
  7. pmc Critical role of VCP/p97 in the pathogenesis and progression of non-small cell lung carcinoma
    Christopher W Valle
    Department of Pediatric Respiratory Sciences, The Johns Hopkins School of Medicine, Baltimore, Maryland, USA
    PLoS ONE 6:e29073. 2011
    Valosin-containing protein (VCP)/p97 is an AAA ATPase molecular chaperone that regulates vital cellular functions and protein-processing...
  8. pmc The role of the N-domain in the ATPase activity of the mammalian AAA ATPase p97/VCP
    Hajime Niwa
    Centre for Structural Biology, Division of Molecular Biosciences, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, United Kingdom
    J Biol Chem 287:8561-70. 2012
    p97/valosin-containing protein (VCP) is a type II ATPase associated with various cellular activities that forms a homohexamer with each protomer containing an N-terminal domain (N-domain); two ATPase domains, D1 and D2; and a disordered ..
  9. ncbi ATPase activity of p97/valosin-containing protein is regulated by oxidative modification of the evolutionally conserved cysteine 522 residue in Walker A motif
    Masakatsu Noguchi
    Laboratory of Functional Biology, Kyoto University Graduate School of Biostudies and Solution Oriented Research for Science and Technology JST, Kyoto 606 8501, Japan
    J Biol Chem 280:41332-41. 2005
    ..Furthermore, a yeast mutant (delta cdc48 + cdc48[T532C]) was shown to be susceptible to oxidants-induced growth inhibition and cell death...
  10. ncbi Novel VCP mutations in inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia
    G D J Watts
    Division of Genetics, Children s Hospital Boston, Harvard Medical School, Boston, MA, USA
    Clin Genet 72:420-6. 2007
    Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia (IBMPFD, OMIM 167320) has recently been attributed to eight missense mutations in valosin-containing protein (VCP)...
  11. pmc Identification of components of the murine histone deacetylase 6 complex: link between acetylation and ubiquitination signaling pathways
    D Seigneurin-Berny
    Laboratoire de Biologie Moléculaire et Cellulaire de la Différenciation, INSERM U309, Equipe chromatine et expression des gènes, Institut Albert Bonniot, Faculte de Medecine, Domaine de la Merci, 38706 La Tronche Cedex, France
    Mol Cell Biol 21:8035-44. 2001
    ..homologues of yeast proteins known to interact with each other and involved in the ubiquitin signaling pathway: p97/VCP/Cdc48p, a homologue of yeast Cdc48p, and phospholipase A2-activating protein, a homologue of yeast UFD3 (..
  12. ncbi Gp78, a membrane-anchored ubiquitin ligase, associates with Insig-1 and couples sterol-regulated ubiquitination to degradation of HMG CoA reductase
    Bao Liang Song
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    Mol Cell 19:829-40. 2005
    ..In addition, gp78 couples regulated ubiquitination to degradation of reductase by binding to VCP, an ATPase that plays a key role in recognition and degradation of ERAD substrates...
  13. pmc Human Fas-associated factor 1, interacting with ubiquitinated proteins and valosin-containing protein, is involved in the ubiquitin-proteasome pathway
    Eun Joo Song
    Center for Cell Signaling Research, Division of Molecular Life Sciences and College of Pharmacy, Ewha Womans University, Seoul 120 750, South Korea
    Mol Cell Biol 25:2511-24. 2005
    ..We investigated the cellular functions of hFAF1 and found that valosin-containing protein (VCP), the multiubiquitin chain-targeting factor in the degradation of the ubiquitin-proteasome pathway, is a binding ..
  14. ncbi An Italian family with inclusion-body myopathy and frontotemporal dementia due to mutation in the VCP gene
    Teresa Gidaro
    Department of Neuroscience, Catholic University, L go A Gemelli 8, 00168 Rome, Italy
    Muscle Nerve 37:111-4. 2008
    Mutations of the valosin-containing protein gene (VCP) are responsible for autosomal-dominant hereditary inclusion-body myopathy associated with frontotemporal dementia and Paget's disease of bone. We identified the p...
  15. doi UBXD1 binds p97 through two independent binding sites
    Maximilian Kern
    Max Planck Institute of Biochemistry, Department of Molecular Cell Biology, Am Klopferspitz 18, 82152 Martinsried, Germany
    Biochem Biophys Res Commun 380:303-7. 2009
    The chaperone-related p97 protein plays a central role in various cellular processes involving the ubiquitin-proteasome system...
  16. pmc Transmembrane domain determinants of CD4 Downregulation by HIV-1 Vpu
    Javier G Magadán
    Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA
    J Virol 86:757-72. 2012
    ..of Vpu into an inactive, oligomeric form and to promote CD4 polyubiquitination and subsequent recruitment of the VCP-UFD1L-NPL4 dislocase complex...
  17. pmc The ubiquitin regulatory X (UBX) domain-containing protein TUG regulates the p97 ATPase and resides at the endoplasmic reticulum-golgi intermediate compartment
    Charisse M Orme
    Section of Endocrinology and Metabolism, Department of Internal Medicine, University School of Medicine, New Haven, Connecticut 06520 8020, USA
    J Biol Chem 287:6679-92. 2012
    b>p97/VCP is a hexameric ATPase that is coupled to diverse cellular processes, such as membrane fusion and proteolysis. How p97 activity is regulated is not fully understood...
  18. pmc Complex of Fas-associated factor 1 (FAF1) with valosin-containing protein (VCP)-Npl4-Ufd1 and polyubiquitinated proteins promotes endoplasmic reticulum-associated degradation (ERAD)
    Jae Jin Lee
    Center for Cell Signaling and Drug Discovery Research, College of Pharmacy, Division of Life and Pharmaceutical Sciences, Department of Bioinspired Science, Ewha Womans University, Seoul 120 750, Korea
    J Biol Chem 288:6998-7011. 2013
    ..to recruit polyubiquitinated proteins and that a C-terminal UBX domain interacts with valosin-containing protein (VCP)...
  19. pmc Caveolin-1 interacts with Derlin-1 and promotes ubiquitination and degradation of cyclooxygenase-2 via collaboration with p97 complex
    Shu Fen Chen
    From the Cardiovascular Division, Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan
    J Biol Chem 288:33462-9. 2013
    ..Here, we identified Cav-1 as a key player in Derlin-1- and p97-mediated cyclooxygenase 2 (COX-2) ubiquitination and degradation...
  20. pmc Structural basis for ovarian tumor domain-containing protein 1 (OTU1) binding to p97/valosin-containing protein (VCP)
    Su Jin Kim
    From the Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136 791, Republic of Korea
    J Biol Chem 289:12264-74. 2014
    Valosin-containing protein (VCP), also known as p97, is an AAA(+) ATPase that plays an essential role in a broad array of cellular processes including the endoplasmic reticulum-associated degradation (ERAD) pathway...
  21. ncbi Derlin-1 promotes the efficient degradation of the cystic fibrosis transmembrane conductance regulator (CFTR) and CFTR folding mutants
    Fei Sun
    Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Biol Chem 281:36856-63. 2006
    A complex involving Derlin-1 and p97 mediates the retrotranslocation and endoplasmic reticulum (ER)-associated degradation of misfolded proteins in yeast and is used by certain viruses to promote host cell protein degradation (Romisch, K...
  22. ncbi VCP (p97) regulates NFkappaB signaling pathway, which is important for metastasis of osteosarcoma cell line
    Tatsuya Asai
    Department of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka 565 0871, Japan
    Jpn J Cancer Res 93:296-304. 2002
    ..SSH revealed expression of the gene encoding valosin-containing protein (VCP; also known as p97) to be constitutively activated in LM8 cells, but it declined in Dunn cells when the cells ..
  23. pmc Ataxin-3 interactions with rad23 and valosin-containing protein and its associations with ubiquitin chains and the proteasome are consistent with a role in ubiquitin-mediated proteolysis
    Ellen W Doss-Pepe
    Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854, USA
    Mol Cell Biol 23:6469-83. 2003
    ..ataxin-3 associates with the ubiquitin- and proteasome-binding factors Rad23 and valosin-containing protein (VCP/p97), findings that support the hypothesis that ataxin-3 is a proteasome-associated factor that mediates the ..
  24. pmc Hereditary inclusion body myopathy-linked p97/VCP mutations in the NH2 domain and the D1 ring modulate p97/VCP ATPase activity and D2 ring conformation
    Dalia Halawani
    The Nicholas Conor Institute for Pediatric Cancer Research, 9710 Scranton Road, Suite 170, San Diego, CA 92121, USA
    Mol Cell Biol 29:4484-94. 2009
    ..dementia (hIBMPFTD) is a degenerative disorder caused by single substitutions in highly conserved residues of p97/VCP. All mutations identified thus far cluster within the NH(2) domain or the D1 ring, which are both required for ..
  25. ncbi Characterization of erasin (UBXD2): a new ER protein that promotes ER-associated protein degradation
    Jing Liang
    Graduate Program in Molecular Medicine, and Institute for Neurodegenerative Diseases, University of Maryland Biotechnology Institute, 725 West Lombard Street, Baltimore, MD 21201, USA
    J Cell Sci 119:4011-24. 2006
    Ubiquitin regulator-X (UBX) is a discrete protein domain that binds p97/valosin-containing protein (VCP), a molecular chaperone involved in diverse cell processes, including endoplasmic-reticulum-associated protein degradation (ERAD)...
  26. pmc HIV-1 Vpu neutralizes the antiviral factor Tetherin/BST-2 by binding it and directing its beta-TrCP2-dependent degradation
    Bastien Mangeat
    Department of Dermatology and Venereology, University Hospitals and Medical School of Geneva, University of Geneva, Switzerland
    PLoS Pathog 5:e1000574. 2009
    ..Identification of tetherin binding to Vpu provides a potential novel target for the development of drugs aimed at inhibiting HIV-1 replication...
  27. ncbi AAA ATPase p97/valosin-containing protein interacts with gp78, a ubiquitin ligase for endoplasmic reticulum-associated degradation
    Xiaoyan Zhong
    Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, Maryland 21201, USA
    J Biol Chem 279:45676-84. 2004
    ..AAA ATPase (ATPase associated with various cellular activities) p97/valosin-containing protein (VCP) subsequently dislodges the ubiquitinated proteins from the ER and chaperones them to the cytosol, where they ..
  28. ncbi Inclusion body myopathy and Paget disease is linked to a novel mutation in the VCP gene
    D Haubenberger
    Department of Neurology, Medical University of Vienna, Vienna, Austria
    Neurology 65:1304-5. 2005
    ..to be associated with hereditary inclusion body myopathy, Paget disease of the bone, and frontotemporal dementia (IBMPFD)...
  29. pmc Unsaturated fatty acids inhibit proteasomal degradation of Insig-1 at a postubiquitination step
    Joon No Lee
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Biol Chem 283:33772-83. 2008
    ..The current study provides a molecular mechanism for regulation of proteasome-mediated ER protein degradation at a postubiquitination step...
  30. pmc Valosin containing protein associated inclusion body myopathy: abnormal vacuolization, autophagy and cell fusion in myoblasts
    Jouni Vesa
    Department of Pediatrics, Division of Genetics and Metabolism, University of California, Irvine, CA 92868, USA
    Neuromuscul Disord 19:766-72. 2009
    Inclusion body myopathy associated with Paget's disease and frontotemporal dementia (IBMPFD) is caused by mutations in the valosin containing protein (VCP) gene...
  31. pmc Dual role of ancient ubiquitous protein 1 (AUP1) in lipid droplet accumulation and endoplasmic reticulum (ER) protein quality control
    Elizabeth J Klemm
    Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
    J Biol Chem 286:37602-14. 2011
    ..These findings indicate a possible connection between ER protein quality control and lipid droplets...
  32. ncbi An NSF-like ATPase, p97, and NSF mediate cisternal regrowth from mitotic Golgi fragments
    C Rabouille
    Cell Biology Laboratory, Imperial Cancer Research Fund, London, England
    Cell 82:905-14. 1995
    ..Pretreatment with NEM or salt washing inhibited regrowth, but this could be restored either by p97, an NSF-like ATPase, or by NSF together with SNAPs and p115, a vesicle docking protein...
  33. ncbi Identification of the cell cycle regulator VCP (p97/CDC48) as a substrate of the band 4.1-related protein-tyrosine phosphatase PTPH1
    S H Zhang
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
    J Biol Chem 274:17806-12. 1999
    ..primarily a 97-kDa tyrosine-phosphorylated protein, which was determined to be VCP (also named p97 or yeast CDC48), from various cell lysates in vitro...
  34. ncbi Elevated expression of valosin-containing protein (p97) in hepatocellular carcinoma is correlated with increased incidence of tumor recurrence
    Shinji Yamamoto
    Departments of Surgery and Clinical Oncology, and Pathology, Osaka University Graduate School of Medicine, Osaka, Japan
    J Clin Oncol 21:447-52. 2003
    Valosin-containing protein (VCP; also known as p97) has been shown to be associated with antiapoptotic function and metastasis via activation of the nuclear factor-kappaB signaling pathway...
  35. ncbi Valosin-containing protein phosphorylation at Ser784 in response to DNA damage
    Mark Livingstone
    Cell Signaling Technology, Inc, Beverly, Massachusetts, USA
    Cancer Res 65:7533-40. 2005
    ..These include histone H2AX and DNA-PK itself. We identify here valosin-containing protein (VCP) as a novel substrate of DNA-PK and other PIKK family members...
  36. ncbi Sequential quality-control checkpoints triage misfolded cystic fibrosis transmembrane conductance regulator
    J Michael Younger
    Department of Cell and Developmental Biology, UNC Chapel Hill School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA
    Cell 126:571-82. 2006
    ..Thus, the RMA1 and CHIP E3 ubiquitin ligases act sequentially in ER membrane and cytosol to monitor the folding status of CFTR and CFTR Delta F508...
  37. pmc Valosin-containing protein (p97) is a regulator of endoplasmic reticulum stress and of the degradation of N-end rule and ubiquitin-fusion degradation pathway substrates in mammalian cells
    Cezary Wojcik
    Department of Anatomy and Cell Biology, Indiana University School of Medicine, Evansville, IN 47712, USA
    Mol Biol Cell 17:4606-18. 2006
    Valosin-containing protein (VCP; p97; cdc48 in yeast) is a hexameric ATPase of the AAA family (ATPases with multiple cellular activities) involved in multiple cellular functions, including degradation of proteins by the ubiquitin (Ub)-..
  38. ncbi The role of a novel p97/valosin-containing protein-interacting motif of gp78 in endoplasmic reticulum-associated degradation
    Petek Ballar
    Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, Maryland 21201, USA
    J Biol Chem 281:35359-68. 2006
    ..Dislocation requires a subclass of ubiquitin ligases that includes gp78 in addition to the AAA ATPase p97/VCP and its cofactor, the Ufd1-Npl4 dimer. We have previously reported that gp78 interacts directly with p97/VCP...
  39. ncbi Identification of SVIP as an endogenous inhibitor of endoplasmic reticulum-associated degradation
    Petek Ballar
    University of Maryland Biotechnology Institute, 725 W Lombard Street, Baltimore, MD 21201, USA
    J Biol Chem 282:33908-14. 2007
    ..To test this hypothesis, we investigated the potential regulatory role of the small p97/VCP-interacting protein (SVIP) on the formation of the ERAD machinery that includes ubiquitin ligase gp78, AAA ATPase ..
  40. pmc Inhibition of p97-dependent protein degradation by Eeyarestatin I
    Qiuyan Wang
    Laboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 283:7445-54. 2008
    ..the action of ubiquitinating enzymes, which polyubiquitinate substrates emerging from the ER lumen, and of the p97-Ufd1-Npl4 ATPase complex, which hydrolyzes ATP to dislocate polyubiquitinated substrates into the cytosol...
  41. pmc An endoplasmic reticulum (ER) membrane complex composed of SPFH1 and SPFH2 mediates the ER-associated degradation of inositol 1,4,5-trisphosphate receptors
    Margaret M P Pearce
    Departments of Pharmacology and Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, New York 13210, USA
    J Biol Chem 284:10433-45. 2009
    ..We propose that this novel SPFH1/2 complex is a recognition factor that targets IP(3)Rs and perhaps other substrates for ERAD...
  42. doi Clearance of Rhodopsin(P23H) aggregates requires the ERAD effector VCP
    Ana Griciuc
    Department of Protein Science, Helmholtz Zentrum Muenchen German Research Center for Environmental Health GmbH, 85764 Neuherberg, Germany
    Biochim Biophys Acta 1803:424-34. 2010
    ..mammalian cell cultures, we provide the first evidence that misfolded Rh(P23H) is a substrate of the ERAD effector VCP, an ATP-dependent chaperone that extracts misfolded proteins from the ER and escorts them for proteasomal ..
  43. pmc Huntingtin interacts with the cue domain of gp78 and inhibits gp78 binding to ubiquitin and p97/VCP
    Hui Yang
    Center for Biomedical Engineering and Technology, University of Maryland, Baltimore, Maryland, United States of America
    PLoS ONE 5:e8905. 2010
    ..competitively reduces polyubiquitinated protein binding to gp78 and also sterically blocks gp78 interaction of p97/VCP, a molecular chaperone that is essential for ERAD...
  44. pmc Valosin-containing protein (VCP) in novel feedback machinery between abnormal protein accumulation and transcriptional suppression
    Masaaki Koike
    Laboratory of Functional Biology, Kyoto University Graduate School of Biostudies and Solution Oriented Research for Science and Technology, Kyoto 606 8501, Japan
    J Biol Chem 285:21736-49. 2010
    ..Genetic and biochemical analyses indicate that valosin-containing protein (VCP) is a crucial molecule in the pathogenesis of human neurodegenerative disorders...
  45. pmc Multilayered mechanism of CD4 downregulation by HIV-1 Vpu involving distinct ER retention and ERAD targeting steps
    Javier G Magadán
    Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS Pathog 6:e1000869. 2010
    ..we find that CD4 degradation induced by Vpu is dependent on a key component of the ERAD machinery, the VCP-UFD1L-NPL4 complex, as well as on SCF(beta-TrCP)-dependent ubiquitination of the CD4 cytosolic tail on lysine and ..
  46. pmc Cellular functions of Ufd2 and Ufd3 in proteasomal protein degradation depend on Cdc48 binding
    Stefanie Böhm
    Department of Biochemistry, Biocenter, University of Wurzburg, Am Hubland, 97074 Wurzburg, Germany
    Mol Cell Biol 31:1528-39. 2011
    The chaperone-related AAA ATPase Cdc48 (p97/VCP in higher eukaryotes) segregates ubiquitylated proteins for subsequent degradation by the 26S proteasome or for nonproteolytic fates...
  47. pmc DNA damage modulates nucleolar interaction of the Werner protein with the AAA ATPase p97/VCP
    Juneth Joaquin Partridge
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Mol Biol Cell 14:4221-9. 2003
    We report a novel nucleolar interaction between the AAA ATPase p97/VCP and the Werner protein (WRNp), a member of the RecQ helicase family...
  48. pmc Pre-B-cell leukemia transcription factor 1 regulates expression of valosin-containing protein, a gene involved in cancer growth
    Ying Qiu
    Department of Pathology, Medical School of Tongji University, Shanghai, China
    Am J Pathol 170:152-9. 2007
    Valosin-containing protein (VCP) is involved in a wide variety of cellular functions. Our previous studies showed that the enhanced expression of VCP in cancer cells correlated with invasion and metastasis of cancers...
  49. ncbi Proteomic characterization of protein phosphatase 1 complexes in ischemia-reperfusion and ischemic tolerance
    Cristina Cid
    Department of Investigation, Hospital Ramon y Cajal, Madrid, Spain
    Proteomics 7:3207-18. 2007
    ..It supports a potential role of PP1 in IR stress and as a target of the endogenous protective mechanisms induced by IT...
  50. ncbi Derlin-1 and p97/valosin-containing protein mediate the endoplasmic reticulum-associated degradation of human V2 vasopressin receptors
    Isabel Schwieger
    Leibniz Institut fur Molekulare Pharmakologie FMP, Campus Buch, Robert Rossle Str 10, 13125 Berlin, Germany
    Mol Pharmacol 73:697-708. 2008
    ..for the first time that V2R mutants with different misfolded domains are able to coprecipitate the ERAD components p97/valosin-containing protein, Derlin-1 and the 26S proteasome regulatory subunit 7...
  51. ncbi Physical and functional interaction between Dorfin and Valosin-containing protein that are colocalized in ubiquitylated inclusions in neurodegenerative disorders
    Shinsuke Ishigaki
    Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya 466 8500, Japan
    J Biol Chem 279:51376-85. 2004
    ..Here we report that Valosin-containing protein (VCP) directly binds to Dorfin and that VCP ATPase activity profoundly contributes to the E3 activity of Dorfin...
  52. ncbi VCP, a weak ATPase involved in multiple cellular events, interacts physically with BRCA1 in the nucleus of living cells
    H Zhang
    Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia 19104 6082, USA
    DNA Cell Biol 19:253-63. 2000
    ..Here, we demonstrate that the BRCA1 protein physically associates with valosin-containing protein (VCP), a member of the ATPases associated with a variety of cellular activities (AAA) superfamily...
  53. ncbi Expression of valosin-containing protein in colorectal carcinomas as a predictor for disease recurrence and prognosis
    Shinji Yamamoto
    Department of Surgery and Clinical Oncology, Osaka University Graduate School of Medicine, Osaka, Japan
    Clin Cancer Res 10:651-7. 2004
    Valosin-containing protein (VCP or p97) is associated with antiapoptotic function and metastasis via activation of the nuclear factor-kappaB signaling pathway...
  54. doi Differential regulation of CFTRDeltaF508 degradation by ubiquitin ligases gp78 and Hrd1
    Petek Ballar
    Ege University, Faculty of Pharmacy, Izmir, 35100, Turkey
    Int J Biochem Cell Biol 42:167-73. 2010
    ..gp78 facilitates the degradation of CFTRDeltaF508 by enhancing both its ubiquitination and interaction with p97/VCP. SVIP, which is the inhibitor of gp78, causes accumulation of CFTRDeltaF508...
  55. ncbi Valosin-containing protein, VCP, is a ubiquitous clathrin-binding protein
    I T Pleasure
    Department of Pharmacology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107
    Nature 365:459-62. 1993
    ..The 100K protein has been identified as valosin-containing protein (VCP; ref. 1), an early substrate for tyrosine phosphorylation on T-cell receptor activation...
  56. ncbi Syntaxin 5 is a common component of the NSF- and p97-mediated reassembly pathways of Golgi cisternae from mitotic Golgi fragments in vitro
    C Rabouille
    Cell Biology Laboratory, Imperial Cancer Research Fund, London, United Kingdom
    Cell 92:603-10. 1998
    A cell-free system that mimics the reassembly of Golgi stacks at the end of mitosis requires two ATPases, NSF and p97, to rebuild Golgi cisternae...
  57. ncbi Clinical and molecular studies in a unique family with autosomal dominant limb-girdle muscular dystrophy and Paget disease of bone
    V E Kimonis
    Department of Pediatircs, Southern Illinois University School of Medicine, Springfield 62794 9658, USA
    Genet Med 2:232-41. 2000
    ..To characterize the clinical features and perform linkage analysis of candidate loci in a large Illinois family with autosomal dominant limb-girdle muscular dystrophy (LGMD) and Paget disease of bone (PDB)...
  58. ncbi Valosin-containing protein is a multi-ubiquitin chain-targeting factor required in ubiquitin-proteasome degradation
    R M Dai
    Intramural Research Support Program, SAIC Frederick, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA
    Nat Cell Biol 3:740-4. 2001
    ..We have shown previously that valosin-containing protein (VCP) physically and functionally targets the ubiquitinated nuclear factor kappaB inhibitor, IkappaBalpha to the ..
  59. ncbi Functional ATPase activity of p97/valosin-containing protein (VCP) is required for the quality control of endoplasmic reticulum in neuronally differentiated mammalian PC12 cells
    Taeko Kobayashi
    Graduate School of Biostudies, Kyoto University, Kyoto, 606 8501, Japan
    J Biol Chem 277:47358-65. 2002
    ..We previously identified p97/valosin-containing protein (VCP), an AAA ATPase with two conserved ATPase domains (D1 and D2), as an interacting partner of the Machado-Joseph ..
  60. pmc VCIP135, a novel essential factor for p97/p47-mediated membrane fusion, is required for Golgi and ER assembly in vivo
    Keiji Uchiyama
    Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 2XY, United Kingdom
    J Cell Biol 159:855-66. 2002
    NSF and p97 are ATPases required for the heterotypic fusion of transport vesicles with their target membranes and the homotypic fusion of organelles...
  61. pmc SVIP is a novel VCP/p97-interacting protein whose expression causes cell vacuolation
    Masami Nagahama
    School of Life Science, Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo 192 0392, Japan
    Mol Biol Cell 14:262-73. 2003
    b>VCP/p97 is involved in a variety of cellular processes, including membrane fusion and ubiquitin-dependent protein degradation. It has been suggested that adaptor proteins such as p47 and Ufd1p confer functional versatility to VCP/p97...
  62. ncbi D1 ring is stable and nucleotide-independent, whereas D2 ring undergoes major conformational changes during the ATPase cycle of p97-VCP
    Qing Wang
    Basic Research Laboratory, Science Applications International Corporation Frederick, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702, USA
    J Biol Chem 278:32784-93. 2003
    The 97-kDa valosin-containing protein (p97-VCP) belongs to the AAA (ATPases associated with various cellular activities) family and acts as a molecular chaperone in diverse cellular events, including ubiquitinproteasome-mediated ..
  63. ncbi A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol
    Yihong Ye
    Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nature 429:841-7. 2004
    ..recognition of a substrate in the ER lumen and its subsequent movement through the membrane by the cytosolic p97 ATPase. Here we identify a p97-interacting membrane protein complex in the mammalian ER that links these two events...
  64. ncbi The AAA ATPase p97/VCP interacts with its alternative co-factors, Ufd1-Npl4 and p47, through a common bipartite binding mechanism
    Roland M Bruderer
    Swiss Federal School of Technology, Institute of Biochemistry, ETH Honggerberg HPM, Zurich 8093, Switzerland
    J Biol Chem 279:49609-16. 2004
    The AAA ATPase p97/VCP forms complexes with different adapters to fulfill distinct cellular functions...
  65. ncbi Valosin-containing protein (p97) and Ki-67 expression is a useful marker in detecting malignant behavior of pancreatic endocrine neoplasms
    Shinji Yamamoto
    Department of Surgery and Clinical Oncology, Osaka University Graduate School of Medicine, Yamadaoka, Suita City, Japan
    Oncology 66:468-75. 2004
    To determine the prognostic value of valosin-containing protein (VCP) expression and the Ki-67 labeling index (LI) in pancreatic endocrine neoplasms (PENs), the present analysis was employed.
  66. ncbi Mutant valosin-containing protein causes a novel type of frontotemporal dementia
    Rolf Schroder
    Department of Neurology, University Hospital Bonn, Sigmund Freud Strasse 25, 53105 Bonn, Germany
    Ann Neurol 57:457-61. 2005
    ..myopathy and frontotemporal dementia who harbors a heterozygous R155C missense mutation residing in the N-terminal CDC48 domain of VCP, which is involved in ubiquitin binding...
  67. ncbi The ubiquitin-domain protein HERP forms a complex with components of the endoplasmic reticulum associated degradation pathway
    Andrea Schulze
    Charite, Universitaetsmedizin Berlin, Campus Charite Mitte, Institut für Biochemie Monbijoustr 2, 10117 Berlin, Germany
    J Mol Biol 354:1021-7. 2005
    ..ubiquitin domain protein (UDP) HERP, the ubiquitin protein ligase HRD1, as well as the retro-translocation factors p97, Derlin-1 and VIMP...
  68. pmc Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response and are required for ER-associated degradation
    Yukako Oda
    Department of Molecular and Cellular Biology Institute for Frontier Medical Sciences, Graduate School of Science, Kyoto University, Sakyo ku, Kyoto 606 8502, Japan
    J Cell Biol 172:383-93. 2006
    ..Derlin-2 and -3 are associated with EDEM and p97, a cytosolic ATPase responsible for extraction of ERAD substrates...
  69. pmc An arginine/lysine-rich motif is crucial for VCP/p97-mediated modulation of ataxin-3 fibrillogenesis
    Annett Boeddrich
    Department of Neuroproteomics, Max Delbrueck Center for Molecular Medicine MDC, Berlin, Germany
    EMBO J 25:1547-58. 2006
    ..protein ataxin-3 (Atx-3) serves as a recognition site for the interaction with the molecular chaperone VCP. Through this interaction, VCP modulates the fibrillogenesis of pathogenic forms of Atx-3 in a concentration-..
  70. ncbi The valosin-containing protein (VCP) is a target of Akt signaling required for cell survival
    Franck Vandermoere
    ERI 8 INSERM, Growth factor signaling in breast cancer Functional proteomics, University of Sciences and Technologies Lille, 59655 Villeneuve d Ascq, France
    J Biol Chem 281:14307-13. 2006
    ..We show, using a proteomics-based approach, that the valosin-containing protein (VCP), a member of the AAA (ATPases associated with a variety of cellular activities) family, is a target of Akt ..
  71. ncbi Endoplasmic reticulum vacuolization and valosin-containing protein relocalization result from simultaneous hsp90 inhibition by geldanamycin and proteasome inhibition by velcade
    Edward G Mimnaugh
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, 9000 Rockville Pike, Building 10, Room 1 5940, Bethesda, MD 20892 1107, USA
    Mol Cancer Res 4:667-81. 2006
    ..lumen are cleared by ER--associated protein degradation, a sequential process requiring valosin-containing protein (VCP)-dependent retrotranslocation followed by ubiquitination and proteasomal proteolysis...
  72. ncbi Mutations in p97/VCP induce unfolding activity
    Andrea Rothballer
    Max Planck Institute of Biochemistry, Department of Molecular Structural Biology, Am Klopferspitz 18, 82152 Martinsried, Germany
    FEBS Lett 581:1197-201. 2007
    ..In contrast, none of the members of the eukaryotic p97/VCP protein family has an aromatic residue in the D1 pore...
  73. ncbi Valosin-containing protein and the pathogenesis of frontotemporal dementia associated with inclusion body myopathy
    Jake B Guinto
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 422 Curie Blvd, 605B Stellar Chance Building, Philadelphia, PA, 19104 6140, USA
    Acta Neuropathol 114:55-61. 2007
    Frontotemporal dementia with inclusion body myopathy and Paget's disease of bone (IBMPFD) is a rare, autosomal dominant disorder caused by mutations in the gene valosin-containing protein (VCP)...
  74. doi Analysis of Npl4 deletion mutants in mammalian cells unravels new Ufd1-interacting motifs and suggests a regulatory role of Npl4 in ERAD
    Agnieszka Lass
    Department of Anatomy and Cell Biology, Indiana University School of Medicine, 8600 University Boulevard, Evansville, IN 47712, USA
    Exp Cell Res 314:2715-23. 2008
    Npl4 is a 67 kDa protein forming a stable heterodimer with Ufd1, which in turn binds the ubiquitous p97/VCP ATPase...
  75. doi Ubxd1 is a novel co-factor of the human p97 ATPase
    Louise Madsen
    Department of Biology, University of Copenhagen, Universitetsparken 13, DK 2100 Copenhagen Ø, Denmark
    Int J Biochem Cell Biol 40:2927-42. 2008
    The AAA ATPase complex known as p97 or VCP in mammals and Cdc48 in yeast is connected to a multitude of cellular pathways, including membrane fusion, protein folding, protein degradation and activation of membrane-bound transcription ..
  76. pmc SEL1L nucleates a protein complex required for dislocation of misfolded glycoproteins
    Britta Mueller
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 105:12325-30. 2008
    ..We identified AUP1, UBXD8, UBC6e, and OS9 as functionally important components of this degradation complex in mammalian cells, as confirmed by mutagenesis and dominant negative versions of these proteins...
  77. pmc UBXD7 binds multiple ubiquitin ligases and implicates p97 in HIF1alpha turnover
    Gabriela Alexandru
    Division of Biology, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA
    Cell 134:804-16. 2008
    b>p97 is an ATP-dependent chaperone that plays an important role in endoplasmic reticulum-associated degradation but whose connections to turnover of soluble proteins remain sparse...
  78. doi Evolutionary divergence of valosin-containing protein/cell division cycle protein 48 binding interactions among endoplasmic reticulum-associated degradation proteins
    Giacomo Morreale
    Laboratory of Molecular Signalling, The Babraham Institute, Cambridge, UK
    FEBS J 276:1208-20. 2009
    ..For example, valosin-containing protein (VCP) and its yeast homologue cell division cycle protein 48 (Cdc48p), which help to direct polyubiquitinated proteins ..
  79. doi A novel mutation in the VCP gene (G157R) in a German family with inclusion-body myopathy with Paget disease of bone and frontotemporal dementia
    Atbin Djamshidian
    Department of Neurology, Medical University of Vienna Währinger Gürtel 18 20, Vienna A 1097, Austria
    Muscle Nerve 39:389-91. 2009
    ..to cause autosomal-dominant inclusion-body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD). We report a novel missense mutation (G157R) in the N-terminal region of the VCP gene in a German family...
  80. pmc Valosin-containing protein (VCP) is required for autophagy and is disrupted in VCP disease
    Jeong Sun Ju
    Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
    J Cell Biol 187:875-88. 2009
    ..protein (VCP) cause inclusion body myopathy (IBM), Paget's disease of the bone, and frontotemporal dementia (IBMPFD)...
  81. pmc Imbalances in p97 co-factor interactions in human proteinopathy
    Vanesa Fernández-Sáiz
    Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany
    EMBO Rep 11:479-85. 2010
    ..in p97 cause the disorder inclusion body myopathy with Paget disease of bone and frontotemporal dementia (IBMPFD)...
  82. pmc The p97 ATPase dislocates MHC class I heavy chain in US2-expressing cells via a Ufd1-Npl4-independent mechanism
    Nia Soetandyo
    Laboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 285:32352-9. 2010
    ..The retrotranslocation also involves the p97 ATPase...
  83. doi Valosin-containing protein cleavage by granzyme K accelerates an endoplasmic reticulum stress leading to caspase-independent cytotoxicity of target tumor cells
    Yuming Guo
    Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
    J Immunol 185:5348-59. 2010
    ..In this study, we found the valosin-containing protein (VCP) is a physiological substrate of GzmK...
  84. pmc Exome sequencing reveals VCP mutations as a cause of familial ALS
    Janel O Johnson
    Neuromuscular Diseases Research Group, Laboratory of Neurogenetics, Porter Neuroscience Building, NIA, NIH, Bethesda, MD 20892, USA
    Neuron 68:857-64. 2010
    ..previously been identified in families with Inclusion Body Myopathy, Paget disease, and Frontotemporal Dementia (IBMPFD)...
  85. pmc The complexities of p97 function in health and disease
    Eli Chapman
    Department of Molecular Biology, The Scripps Research Institute, Skaggs Molecular Biology Building, 10596 Torrey Pines Road, Rm 203, La Jolla, CA 92037, USA
    Mol Biosyst 7:700-10. 2011
    b>p97 is a homohexameric, toroidal machine that harnesses the energy of ATP binding and hydrolysis to effect structural reorganization of a diverse and primarily uncharacterized set of substrate proteins...
  86. pmc The p97 ATPase associates with EEA1 to regulate the size of early endosomes
    Harish N Ramanathan
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Cell Res 22:346-59. 2012
    The AAA (ATPase-associated with various cellular activities) ATPase p97 acts on diverse substrate proteins to partake in various cellular processes such as membrane fusion and endoplasmic reticulum-associated degradation (ERAD)...
  87. doi Cdc48: a power machine in protein degradation
    Alexandra Stolz
    Institute for Biochemistry, University of Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany
    Trends Biochem Sci 36:515-23. 2011
    b>Cdc48 is an essential, highly prominent ATP driven machine in eukaryotic cells...
  88. pmc Endolysosomal sorting of ubiquitylated caveolin-1 is regulated by VCP and UBXD1 and impaired by VCP disease mutations
    Danilo Ritz
    Centre for Medical Biotechnology, University of Duisburg Essen, 45117 Essen, Germany
    Nat Cell Biol 13:1116-23. 2011
    The AAA-ATPase VCP (also known as p97) cooperates with distinct cofactors to process ubiquitylated proteins in different cellular pathways...
  89. pmc The tissue-specific Rep8/UBXD6 tethers p97 to the endoplasmic reticulum membrane for degradation of misfolded proteins
    Louise Madsen
    Department of Biology, University of Copenhagen, Copenhagen, Denmark
    PLoS ONE 6:e25061. 2011
    The protein known as p97 or VCP in mammals and Cdc48 in yeast is a versatile ATPase complex involved in several biological functions including membrane fusion, protein folding, and activation of membrane-bound transcription factors...
  90. doi Characterization of the Asian myopathy patients with VCP mutations
    Z Shi
    Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry NCNP, Kodaira, Tokyo, Japan
    Eur J Neurol 19:501-9. 2012
    ..VCP) gene are known to cause inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD) and familial amyotrophic lateral sclerosis (ALS)...
  91. pmc Distinct conformations of the protein complex p97-Ufd1-Npl4 revealed by electron cryomicroscopy
    Cecilia Bebeacua
    Centre for Structural Biology and Centre for Biomolecular Electron Microscopy, Division of Molecular Biosciences, Imperial College London, London SW7 2AZ, United Kingdom
    Proc Natl Acad Sci U S A 109:1098-103. 2012
    b>p97 is a key regulator of numerous cellular pathways and associates with ubiquitin-binding adaptors to remodel ubiquitin-modified substrate proteins...
  92. doi Emerging functions of the VCP/p97 AAA-ATPase in the ubiquitin system
    Hemmo Meyer
    Centre for Medical Biotechnology, Faculty of Biology, University of Duisburg Essen, 45117 Essen, Germany
    Nat Cell Biol 14:117-23. 2012
    The ATP-driven chaperone valosin-containing protein (VCP)/p97 governs critical steps in ubiquitin-dependent protein quality control and intracellular signalling pathways...
  93. doi Increased expression of valosin-containing protein in the skin of patients with amyotrophic lateral sclerosis
    Hiroaki Ishikawa
    Department of Neurology, Teikyo University Chiba Medical Center, 3426 3 Anesaki, Ichihara, Chiba 299 0111, Japan
    J Clin Neurosci 19:522-6. 2012
    Valosin-containing protein (VCP) may have a pivotal role in ubiquitin-dependent protein degradation and is implicated in the pathogenesis of neurodegenerative diseases...
  94. pmc Interprotomer motion-transmission mechanism for the hexameric AAA ATPase p97
    Guangtao Li
    Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794 5215, USA
    Proc Natl Acad Sci U S A 109:3737-41. 2012
    ..The essential and highly abundant hexameric AAA ATPase p97 is perhaps the best studied AAA protein, playing an essential role in various important cellular activities...
  95. pmc Phenotypic variability in three families with valosin-containing protein mutation
    S Spina
    Department of Pathology and Laboratory Medicine, Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    Eur J Neurol 20:251-8. 2013
    The phenotype of IBMPFD [inclusion body myopathy with Paget's disease of the bone and frontotemporal dementia (FTD)] associated with valosin-containing protein (VCP) mutation is described in three families.
  96. pmc Valosin-containing protein (VCP/p97) is an activator of wild-type ataxin-3
    Mario N Laco
    Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal
    PLoS ONE 7:e43563. 2012
    ..with two proteins previously described to interact with ataxin-3, hHR23A and valosin-containing protein (VCP/p97). We confirmed ataxin-3 affinity for both hHR23A and VCP/p97...
  97. pmc A ubiquitin-like domain recruits an oligomeric chaperone to a retrotranslocation complex in endoplasmic reticulum-associated degradation
    Yue Xu
    Laboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 288:18068-76. 2013
    ..We propose that simultaneous association with multiple ERAD factors helps to anchor a disordered chaperone oligomer to the site of retrotranslocation to prevent protein aggregation in ERAD. ..
  98. pmc Neuronal-specific overexpression of a mutant valosin-containing protein associated with IBMPFD promotes aberrant ubiquitin and TDP-43 accumulation and cognitive dysfunction in transgenic mice
    Carlos J Rodriguez-Ortiz
    School of Natural Sciences, University of California, Merced, California 95343, USA
    Am J Pathol 183:504-15. 2013
    ..dominant disease called inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia (IBMPFD)...
  99. doi Valosin-containing protein immunoreactivity in tauopathies, synucleinopathies, polyglutamine diseases and intranuclear inclusion body disease
    Fumiaki Mori
    Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
    Neuropathology 33:637-44. 2013
    ..body myopathy with Paget's disease and frontotemporal dementia and familial amyotrophic lateral sclerosis (fALS; ALS14), both of which are characterized by trans-activation response DNA protein 43 (TDP-43)-positive neuronal ..
  100. ncbi Involvement of valosin-containing protein, an ATPase Co-purified with IkappaBalpha and 26 S proteasome, in ubiquitin-proteasome-mediated degradation of IkappaBalpha
    R M Dai
    Intramural Research Support Program, SAIC Frederick, NCI Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA
    J Biol Chem 273:3562-73. 1998
    ..We identify valosin-containing protein (VCP), an AAA (ATPases associated with a variety of cellular activities) family member, that co-precipitates with ..
  101. pmc Multiprotein complexes that link dislocation, ubiquitination, and extraction of misfolded proteins from the endoplasmic reticulum membrane
    Brendan N Lilley
    Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:14296-301. 2005
    ..Derlin-1 acts in concert with the AAA ATPase p97 to remove dislocation substrate proteins from the ER membrane, but it is unknown whether other factors aid Derlin-1 ..

Research Grants70

  1. Conrad C Weihl; Fiscal Year: 2016
    ..further by the identification of mutations in the protein p97/VCP that cause the autosomal dominant syndrome, IBMPFD, IBM associated with paget's disease of the bone and frontotemporal dementia (FTD)...
  2. Mariusz Karbowski; Fiscal Year: 2015
    ..Furthermore, we also found that AAA- ATPase p97, a critical protein for the endoplasmic reticulum associated degradation (ERAD) pathway, is essential for both ..
  3. James A Olzmann; Fiscal Year: 2015
    ..identify a metabolically regulated LD ubiquitination pathway that involves UBXD8-mediated recruitment of p97/VCP and regulation LD turnover catalyzed by ATGL, the rate-limiting enzyme in lipolysis...
  4. Defining the role of ubiquitination in the regulation of lipid droplet function
    James A Olzmann; Fiscal Year: 2013
    ..findings identify a metabolically regulated LD ubiquitination pathway that involves UBXD8-mediated recruitment of p97/VCP and regulation LD turnover catalyzed by ATGL, the rate-limiting enzyme in lipolysis...
  5. High-fat diet rescues lethality of homozygous knock-in R155H VCP myopathic mice
    VIRGINIA EUNICE KIMONIS; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Our laboratory was the first to identify VCP mutations as a cause of hereditary inclusion body myopathy, Paget's disease of bone, frontotemporal dementia and amyotrophic lateral sclerosis, and ..
  6. Translational Studies in VCP Inclusion Body Myopathy with Paget Disease of Bone
    Virginia Kimonis; Fiscal Year: 2009
    ..inclusion body myopathy (h-IBM), Paget disease of bone (PDB) and/or frontotemporal dementia (FTD), also called IBMPFD was recognized as a distinct clinical syndrome in 2000 by Kimonis et al...
  7. Changcheng Song; Fiscal Year: 2014
    ..Valosin-containing protein (VCP/p97), a molecular chaperone, lies at the heart of proteostasis to unfold ubiquitinated proteins for proteasomal ..
  8. Cellular Mechanisms of Aggregation of Abnormal Proteins
    Michael Y Sherman; Fiscal Year: 2012
    ..element for the P-region aggresome- targeting signal, (c) a yeast 14-3-3 protein Bmh1 and components of the Cdc48/VCP-Ufd1-Nlp4 complex play an essential role in aggresome formation...
  9. The role of p97 in protein degradation during aging and disease
    EUGENE DROKHLYANSKY; Fiscal Year: 2013
    ..Previous studies support that p97 (known as VCP in metazoans and Cdc48 in yeast) is important for the degradation of damaged and misfolded proteins possibly by preventing their ..
  10. Ubiquitin and Cell Cycle Regulation of Golgi Membrane Dynamics
    Yanzhuang Wang; Fiscal Year: 2013
    ..Reassembly is mediated by two ATPases (NSF and p97) that fuse the membranes...
  11. Exploring mechanisms of TDP-43 aggregation and disaggregation
    James Shorter; Fiscal Year: 2010
    ..We are particularly interested in how two AAA+ ATPases, Hsp104 and p97, might antagonize or reverse TDP-43 aggregation...
  12. Mechanisms of VCP/p97 and Proteasomal pathway in COPD pathogenesis
    Neeraj Vij; Fiscal Year: 2010
    ..protein levels of AAA (ATPase associated with diverse cellular activities) molecular chaperone and UPR modulator, p97/VCP (Valosin containing protein), are significantly upregulated in COPD peripheral lungs of smokers as compared to ..
  13. Alex B Lentsch; Fiscal Year: 2014
    ..The cytoplasmic chaperone, valosin- containing protein (VCP), is known to bind to ubiquitinylated proteins, including IkBa, and facilitate their recruitment to the proteasome...
  14. Jianping Jin; Fiscal Year: 2016
    ..Recent studies in our lab suggest that a valosin-containing protein (VCP) and its cofactor, UFD1L, are involved in post-ubiquitinational regulation of I?B[unreadable]...
  15. Understanding and targeting Nrf1-mediated proteasome recovery pathway in cancer
    SENTHIL KUMAR RADHAKRISHNAN; Fiscal Year: 2012
    ..Specific Aims during the independent phase are designed to understand the role of p97/VCP and its co-factors in Nrf1 activation and to identify novel chemical inhibitors of the Nrf1-mediated proteasome ..
  16. KENNETH R TETER; Fiscal Year: 2016
    ..Most ERAD substrates are extracted from the ER through a mechanism involving the cytosolic AAA ATPase p97. However, p97 appears to play a minimal role in CTA1 translocation...
  17. Role of the Sec61 Translocon in EGF Receptor Trafficking and Signaling
    GRAHAM F CARPENTER; Fiscal Year: 2012
    ..This includes HSP70 and p97, an ATPase that is tyrosine phosphorylated following the addition of EGF...
  18. Nuclear Membrane Fusion in Xenopus Egg Extracts
    Martin W Hetzer; Fiscal Year: 2010
    ..generated new information about the two major regulators of nuclear assembly, the GTPase Ran and the AAA-ATPase p97. Our specific aims are: 1...
  19. SVIP and CMT1A
    Jun Li; Fiscal Year: 2013
    ..SVIP interacts with Valosin-Containing Protein (VCP;also called p97), a highly conserved ATPase that is ubiquitously distributed...
  20. Smallpox vaccine and vaccinia complement control protein
    STUART ISAACS; Fiscal Year: 2009
    ..We hypothesize that the vaccinia complement control protein (VCP) is a virulence factor with both a central role in protecting the virus from innate immunity and an ..
  21. Conrad C Weihl; Fiscal Year: 2016
    ..One age associated muscle disorder is due to mutations in valosin containing protein (VCP) which causes IBMPFD or inclusion body myopathy (IBM) associated with Paget's disease of the bone (PDB) and fronto-temporal ..
  22. Fen Biao Gao; Fiscal Year: 2016
    ..Indeed, several genes, including CHMP2B, VCP, TDP-43, FUS, Ubiquilin 2, and C9ORF72, have been implicated in the molecular pathogenesis of both diseases...
  23. CYTOPLASMIC FACTORS IN NUCLEAR PROTEIN IMPORT
    Stephen Adam; Fiscal Year: 2000
    ..Cytoplasmic assembly of a receptor complex composed of two transport factors, p97 and the NLS receptor is believed to precede docking of the complex at the nuclear pore...
  24. Masashi Kitazawa; Fiscal Year: 2014
    ..disorder called inclusion body myopathy associated with Paget disease ofthe bone and frontotemporal dementia (IBMPFD)...
  25. Characterizing the Role of VCP in Paget's Disease of the Bone
    Giles Watts; Fiscal Year: 2009
    ..combination of hereditary inclusion body myopathy, Paget disease of bone and frontotemporal dementia, now called IBMPFD (MIM 605382). I have recently identified the gene for IBMPFD as VCP...
  26. HPV-16 and head and neck cancer
    Thomas Haugen; Fiscal Year: 2013
    ..of the cervix and the head and neck contain and express the viral E6-E7 oncogenic region from a promoter at nt 97 (P97)...
  27. GENETIC BASES FOR DISEASES OF THE RANK SIGNALING PATHWAY
    STEVEN R MUMM; Fiscal Year: 2013
    ..candidate genes in the OPG/RANKL/RANK/NF-?B signaling pathway for disease-causing mutations, including SQSTM1, VCP, TRAF6, aPKC, NIK, and others...
  28. Dihydrodiol dehydrogenase mediates cisplatin resistance
    Henry Simpkins; Fiscal Year: 2007
    ..We propose to continue this work by (a) transfection of non-ovarian cell lines, including Tera-2 (germ cell tumors), A431(cervical carcinoma cells), HTB56 (lung adenocarcinoma ceils) and H69 (small cell lung ..
  29. Influence of Heme on Hepatic Cytochrome P450 Synthesis and Degradation
    Maria Correia; Fiscal Year: 2007
    ..ER extraction requires ATP hydrolysis and thus could involve either the p97 AAA ATPase or the proteasomal 19S AAA ATPases...
  30. BIGDATA: Mid-Scale: DA : Collaborative Research Big Tensor Mining Theory
    Christos Faloutsos; Fiscal Year: 2013
    ..or action-like verbs ('run')? We propose three research thrusts: i) Motivating Applications: Real-world tera-scale applications, including 'read-the-web', NeuroSemanticslarge recommendation systems ii) New theory ..
  31. MEMBRANE FUSION ATPASES AND THE GOLGI APPARATUS
    Ayano Satoh; Fiscal Year: 2007
    ..The last granting period focused on the reassembly of Golgi cisternae that is catalyzed by two ATPases, NSF and p97. NSF was shown to have an activity additional to its well-characterized role in unraveling SNARE complexes...
  32. Study of Interactions of VCP with Complement Components
    Krishna Murthy; Fiscal Year: 2007
    ..Vaccinia Complement Protein (VCP) was one of the first such mimics to be discovered and characterized...
  33. New anti-complement therapy to reduce reperfusion injury
    Claudio Maldonado; Fiscal Year: 2005
    ..to optimize the display of a modified complement blocking protein named vaccinia virus complement control protein (VCP) on the surface of endothelial cells, and show that it can reduce complement induced damage after cells are exposed ..
  34. POXVIRUS SCR-CONTAINING PROTEINS AS THERAPEUTIC TARGETS
    STUART ISAACS; Fiscal Year: 2003
    ..The vaccinia complement-control protein (VCP) and the extracellular enveloped virus (EEV)-specific B5R protein both contain short consensus repeat (SCR) units ..
  35. AB 3730XL, 96 Cap DNA Analyzer
    Mitchell Sogin; Fiscal Year: 2005
    ..The equipment to be purchased includes an Applied Biosystems 3730XL DNA Analyzer and a 3.4 tera-byte data storage system based upon Apple Computer's Xserve RAID and Xserve G5 architecture...
  36. The role of ubiquitination in Legionella pneumophila infection and disease.
    ALEXANDER ENSMINGER; Fiscal Year: 2009
    ..vacuole (LCV) upon infection and a downstream component of the host ubiquitin-mediated proteolytic pathway, Cdc48/p97 is required for efficient intracellular growth of the bacteria. Additionally, the L...
  37. EPIDERMAL TRANS-ACTING FACTORS IN SKIN DEVELOPMENT
    Renata Polakowska; Fiscal Year: 1993
    ..genes and a keratinocyte-dependent (KD) enhancer sequence element of the human papilloma virus-16 (HPV-16) p97 promoter. Viral KD-enhancer activation is restricted to keratinocytes...
  38. MOSQUITO OOCYTES - MECHANISM OF PROTEIN ACCUMULATION
    Alexander Raikhel; Fiscal Year: 2001
    ..In addition, I propose to study the receptor for vitellogenic carboxypeptidase (VCP), another important mosquito yolk protein precursor...
  39. HUMAN PAPILLOMAVIRUS-16 REGULATION IN CERVICAL CANCER
    LUBOMIR TUREK; Fiscal Year: 1991
    ..and viral regulatory factors at the transcriptional promoter of the candidate E6-E7 oncogene region of HPV-16, P97, in transfection and DNA binding studies. Based on our recent data (Cripe et aL, 1987, ref...
  40. Role of Gab2 in Mast Cell Function and Ontogeny
    Haihua Gu; Fiscal Year: 2006
    ..long-term goal of this grant proposal is to understand the mechanism by which the novel scaffolding adapter Gab2/p97 regulates the biological responses of hematopoietic cells...
  41. AAA ATPase p97/VCP and Inclusion Body Myopathy
    CONRAD WEIHL; Fiscal Year: 2009
    ..in p97/VCP cause the autosomal dominantly syndrome HIBM, Paget's Disease and frontotemporal dementia (IBMPFD)...
  42. Validation of a Human In Vitro Vaginal Irritation Test
    Seyoum Ayehunie; Fiscal Year: 2007
    ..agents contained within spermicides, medicaments, microbicides, feminine hygiene and other vaginal care products (VCP) can cause inflammation or tissue damage and thus endanger the health of women...
  43. Evaluation and Application of an Adapted Measure of Inspection Time of Children w
    Seth Warschausky; Fiscal Year: 2009
    ..The first group consists of children who communicate verbally (VCP) and have functional activity levels classified as GMFCS I-III...
  44. MECHANISM OF PLATELET ACTIVATION ON MATRIX PROTEINS
    Beatrice Haimovich; Fiscal Year: 2004
    ..and/or aggregated platelets: a-actinin, vinculin, and a lO1-kD protein (pplOl) that is identical or related to VCP (Valosin-containing protein). Recently we reported that a-actinin is tyrosine phosphorylated in spread platelets...
  45. ROLE OF BAG2 AND SHP2 IN HEMATOPOIETIC SIGNALLING
    BENJAMIN NEEL; Fiscal Year: 2004
    ..During the initial funding period, we identified, purified and cloned p97. p97 is a relative of Gab1 and Drosophila Dos, a regulator of the fly homolog of SHP-2; thus, we renamed p97 as ..
  46. Targeting JAK-3 with WHI-P97 for Treatment of Asthma
    Peter Samuel; Fiscal Year: 2003
    ..designed Janus kinase 3 (JAK3) inhibitor 4-(3',5'-dibromo-4'-hydroxyphenyl)- anmino-6,7-dirnethoxyquinazoline (WHI-P97) exhibits potent in vivo biologic activity in a mouse model of allergic asthma at nontoxic dose levels...
  47. Modeling TDP-43 Dysfunction in vivo
    Zuoshang Xu; Fiscal Year: 2009
    ..protein tau (MAPT), charged multivesicular body protein 2B (CHMP2B), vasolin-containing protein (VCP) and progranulin (PGRN). How these mutant genes cause neuronal degeneration is not known...
  48. HPV16-induced TGF-Beta resistance in human keratinocytes
    KIM CREEK; Fiscal Year: 2006
    ..In addition, the molecular basis for the marked inhibition of HPV16 P97 promoter activity by TGF-beta will be investigated...
  49. PROTEOLYTIC SIGNALING BY POLYUBIQUITIN CHAINS
    Michael Matunis; Fiscal Year: 2006
    ..rate and pathway of proteasome-dependent degradation and b) how an extraproteasomal chaperone complex containing Cdc48/VCP functions in the degradation of ubiquitin-fused substrates...
  50. THE MOLECULAR NATURE OF TUMOR ANTIGENS
    RICHARD WOODBURY; Fiscal Year: 1980
    ..The other two melanoma-associated antigens are proteins with molecular weights of approximately 97,000 (p97) and 210,000 (p210), respectively...
  51. Single Molecule Studies of SNARE-Induced Vesicle Fusion
    Axel T Brunger; Fiscal Year: 2010
    ..Such a system could serve as an efficient model system for novel drug discovery. ..
  52. GENE CAUSING PAGET & LIMB-GIRDLE MUSCULAR DYSTROPHY
    Virginia Kimonis; Fiscal Year: 2003
    ..Delineation of the genetic component responsible for the LGMD/PDB phenotype should promise similar insight and facilitate in the design of novel treatment protocols for the two disorders. ..
  53. Genetic basis of myopathy with Paget disease of bone
    Virginia Kimonis; Fiscal Year: 2008
    ..of disorders such as limb girdle muscular dystrophy and amyotropic lateral sclerosis has been categorized as IBMPFD (MIM 605382)...
  54. Characterization of Familial Myopathy & Paget Disease
    Virginia Kimonis; Fiscal Year: 2005
    ..of disorders such as limb girdle muscular dystrophy and amyotropic lateral sclerosis has been categorized as IBMPFD (MIM 605382)...
  55. INHIBITION OF OSTEOCLAST ACTIVITY BY OIP-1/HSCAL
    SAKAMURI REDDY; Fiscal Year: 2008
    ..abstract_text> ..
  56. Pathogenic determinants in the SIV envelope transmembrane cytoplasmic domain
    James Hoxie; Fiscal Year: 2007
    ..abstract_text> ..
  57. Parkin mediated Neural Dysfunction in Drosophila
    Leo Pallanck; Fiscal Year: 2004
    ..Results from this work should clarify the relationship between parkin dysfunction and neurodegeneration, and possibly reveal strategies for treatment of Parkinson's disease. ..
  58. The role of hMLH1-hMRE11 in DNA mismatch repair
    Chengtao Her; Fiscal Year: 2007
    ..abstract_text> ..
  59. GENETIC DISSECTION OF DENDRITE DEVELOPMENT
    YUH JAN; Fiscal Year: 2009
    ..The Core programs identified from this work will contribute to the understanding and eventual treatment of human neurological diseases many of which have pathology in dendrites. ..
  60. Mechanisms of Tau-Based Neurodegeneration
    Mark Forman; Fiscal Year: 2005
    ..This proposal will also facilitate my transition from a trainee to a fully independent experimental neuropathologist. ..
  61. High-Throughput Campaign to Identify Reversible Small Molecule Inhibitor of p97/C
    Raymond Deshaies; Fiscal Year: 2008
    unreadable] DESCRIPTION (provided by applicant): p97 is an essential protein that plays a critical role in a number of different cellular processes...
  62. Gene Expression in Inflammatory Myopathies
    Steven Greenberg; Fiscal Year: 2005
    ..This work may provide further diagnostic approaches to these disorders and contribute to the understanding of their pathogenesis. ..
  63. HIV-2 Env Variable Loop Deletions as HIV-1 Vaccines
    George Lin; Fiscal Year: 2006
    ..Two Specific Aims are proposed: #1) engineer HIV-1 converting mutations into wildtype HIV-2/vcp Env and functional, hypervariable loop deleted derivatives and assess for retention of functionality and #2) ..
  64. Proteomic analyses of Drosophila Parkinson's disease model
    Leo Pallanck; Fiscal Year: 2007
    ..This work should clarify the biological role of Parkin and will serve as a foundation for future hypothesis-driven investigation of parkin pathogenesis. [unreadable] [unreadable]..
  65. Pathogenic Determinants of SIV Envelope Glycoproteins
    James Hoxie; Fiscal Year: 2006
    ..Collectively these Aims provide novel approaches for structure-based alterations in the SIV TM that will impact on pathogenesis and the host immune response. ..
  66. Cell Mechanisms of Abnormal Protein Aggregation
    Michael Sherman; Fiscal Year: 2007
    ..Exploration of fundamental mechanisms of protein aggregation that we undertake in this project will help to understand the nature of several neurological disorders. ..
  67. Mtb Proteasome-Associated Factors and Virulence
    KATERINA DARWIN; Fiscal Year: 2007
    ..Taken together it will be important to develop faster acting drugs to new targets in Mtb in order to better treat tuberculosis in the future. ..