Vcp

Summary

Gene Symbol: Vcp
Description: valosin containing protein
Alias: 3110001E05, CDC48, p97, p97/VCP, transitional endoplasmic reticulum ATPase, 15S Mg(2+)-ATPase p97 subunit, AAA ATPase p97, Inv protein, TER ATPase, homolog of yeast cdc48
Species: mouse

Top Publications

  1. 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
  2. ncbi Inclusion body myopathy-associated mutations in p97/VCP impair endoplasmic reticulum-associated degradation
    Conrad C Weihl
    Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Hum Mol Genet 15:189-99. 2006
  3. 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
  4. ncbi Central pore residues mediate the p97/VCP activity required for ERAD
    Byron DeLaBarre
    Howard Hughes Medical Institute, Stanford University, JH Clark Center E300 C, California 94305, USA
    Mol Cell 22:451-62. 2006
  5. ncbi Nucleotide dependent motion and mechanism of action of p97/VCP
    Byron DeLaBarre
    Howard Hughes Medical Institute, and Department of Molecular and Cellular Physiology, and Stanford Synchrotron Radiation Laboratory, Stanford University, J H Clark Center E300 C, 318 Campus Drive, Stanford, CA 94305 5432, USA
    J Mol Biol 347:437-52. 2005
  6. pmc HDAC6-p97/VCP controlled polyubiquitin chain turnover
    Cyril Boyault
    INSERM U309, Laboratoire de Biologie Moléculaire et Cellulaire de la Différenciation, Equipe chromatine et expression des gènes, Institut Albert Bonniot, Faculte de Medecine, Domaine de la Merci, La Tronche, France
    EMBO J 25:3357-66. 2006
  7. ncbi Conformational changes of p97 during nucleotide hydrolysis determined by small-angle X-Ray scattering
    Jason M Davies
    Department of Structural Biology, Stanford University School of Medicine, 299 Campus Drive West, Stanford, California 94305, USA
    Structure 13:183-95. 2005
  8. pmc Regulation of retrotranslocation by p97-associated deubiquitinating enzyme ataxin-3
    Qiuyan Wang
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 174:963-71. 2006
  9. 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
  10. 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

Scientific Experts

  • CONRAD WEIHL
  • Hemmo H Meyer
  • Ogan D Abaan
  • Yukiko Yoshida
  • Tsui Fen Chou
  • B Beirowski
  • Guangtao Li
  • Angele Nalbandian
  • Gang Zhao
  • William J Lennarz
  • Virginia E Kimonis
  • Mallikarjun Badadani
  • Hermann Schindelin
  • Xiaodong Zhang
  • Paul S Freemont
  • Hisao Kondo
  • Akira Kakizuka
  • Katrina J Llewellyn
  • Yihong Ye
  • Chengdong Huang
  • Cyril Boyault
  • Masaaki Koike
  • J Paul Taylor
  • Byron DeLaBarre
  • Jeong Sun Ju
  • Seiji Hori
  • Louise C Briggs
  • Tal Glinka
  • Nickie C Chan
  • Hanako Ohashi Ikeda
  • Aria Eshraghi
  • Xiaoke Zhou
  • Jea Hwang Lee
  • Hongxia Wang
  • N Jiang
  • Jose F Abisambra
  • Paulo Lizano
  • James K Ching
  • Sam Tonddast-Navaei
  • Akansha Tiwari
  • Kyota Fujita
  • Dominik Barthelme
  • Jouni Vesa
  • Christopher Nguyen
  • Cecilia Bebeacua
  • Rosanna Piccirillo
  • Marie Noëlle Laguë
  • Felix Hauler
  • VINCENT CAIOZZO
  • ANDREW L MAMMEN
  • Toshihiro Marutani
  • Jogeshwar Mukherjee
  • Justine P Lu
  • Masashi Kitazawa
  • Hsiao Fang Wang
  • Matthias Zehner
  • Shigetsugu Hatakeyama
  • Ana Griciuc
  • Takashi Ohama
  • Sara K Custer
  • Yayoi Kaneko
  • Jin Mi Heo
  • Koichi Kokame
  • Erich E Wanker
  • Go Totsukawa
  • Sevil Cayli
  • Efrat Rabinovich
  • Gen Sobue
  • Richard J H Wojcikiewicz
  • Ukiko Fujise
  • Genqing Liang
  • Anna L Wilbrey
  • Jane E Haley
  • Giacomo Morreale
  • Robert Adalbert
  • J M M Müller
  • Michael P Coleman
  • Rivka L Isaacson
  • Richard R Ribchester
  • Laura Conforti
  • Thomas M Wishart
  • Patrick Matthias
  • Saadi Khochbin
  • Yu Zhang
  • Benoit Gilquin
  • Heike Laser
  • Qiuyan Wang
  • Annett Boeddrich
  • Axel T Brunger
  • Keyvan Behnam

Detail Information

Publications90

  1. 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...
  2. ncbi Inclusion body myopathy-associated mutations in p97/VCP impair endoplasmic reticulum-associated degradation
    Conrad C Weihl
    Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Hum Mol Genet 15:189-99. 2006
    Mutations in the AAA+ protein (ATPase associated with a variety of cellular activities) p97/VCP (valosin-containing protein) cause a dominantly inherited syndrome of inclusion body myopathy with Paget's disease of the bone and fronto-..
  3. 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-..
  4. ncbi Central pore residues mediate the p97/VCP activity required for ERAD
    Byron DeLaBarre
    Howard Hughes Medical Institute, Stanford University, JH Clark Center E300 C, California 94305, USA
    Mol Cell 22:451-62. 2006
    The AAA-ATPase p97/VCP facilitates protein dislocation during endoplasmic reticulum-associated degradation (ERAD)...
  5. ncbi Nucleotide dependent motion and mechanism of action of p97/VCP
    Byron DeLaBarre
    Howard Hughes Medical Institute, and Department of Molecular and Cellular Physiology, and Stanford Synchrotron Radiation Laboratory, Stanford University, J H Clark Center E300 C, 318 Campus Drive, Stanford, CA 94305 5432, USA
    J Mol Biol 347:437-52. 2005
    ..One of the members of this family, the hexameric p97/valosin-containing protein p97/VCP, is essential for the dislocation of misfolded membrane proteins from the endoplasmic reticulum...
  6. pmc HDAC6-p97/VCP controlled polyubiquitin chain turnover
    Cyril Boyault
    INSERM U309, Laboratoire de Biologie Moléculaire et Cellulaire de la Différenciation, Equipe chromatine et expression des gènes, Institut Albert Bonniot, Faculte de Medecine, Domaine de la Merci, La Tronche, France
    EMBO J 25:3357-66. 2006
    ..We further show that HDAC6-interacting chaperone, p97/VCP, dissociates the HDAC6-ubiquitin complexes and counteracts the ability of HDAC6 to promote the accumulation of ..
  7. ncbi Conformational changes of p97 during nucleotide hydrolysis determined by small-angle X-Ray scattering
    Jason M Davies
    Department of Structural Biology, Stanford University School of Medicine, 299 Campus Drive West, Stanford, California 94305, USA
    Structure 13:183-95. 2005
    Valosin-containing protein (VCP)/p97 is an AAA family ATPase that has been implicated in the removal of misfolded proteins from the endoplasmic reticulum and in membrane fusion...
  8. pmc Regulation of retrotranslocation by p97-associated deubiquitinating enzyme ataxin-3
    Qiuyan Wang
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 174:963-71. 2006
    ..Retrotranslocation of many substrates requires an ATPase complex consisting of the p97 ATPase and a dimeric cofactor, Ufd1-Npl4...
  9. 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 ..
  10. 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...
  11. ncbi Targeted deletion of p97 (VCP/CDC48) in mouse results in early embryonic lethality
    J M M Müller
    Endothelial Cell Biology Laboratory, Cancer Research UK, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Biochem Biophys Res Commun 354:459-65. 2007
    The highly conserved AAA ATPase p97 (VCP/CDC48) has well-established roles in cell cycle progression, proteasome degradation and membrane dynamics...
  12. ncbi Transgenic expression of inclusion body myopathy associated mutant p97/VCP causes weakness and ubiquitinated protein inclusions in mice
    Conrad C Weihl
    Department of Neurology, Washington University School of Medicine, 660 S Euclid Avenue, Saint Louis, MO 63110, USA
    Hum Mol Genet 16:919-28. 2007
    Mutations in p97/VCP cause the autosomal-dominant, inherited syndrome inclusion body myopathy (IBM) associated with Paget's disease of the bone and frontotemporal dementia (IBMPFD) (Watts, G.D., Wymer, J., Kovach, M.J., Mehta, S.G...
  13. pmc Structural basis of the interaction between the AAA ATPase p97/VCP and its adaptor protein p47
    Ingrid Dreveny
    Centre for Structural Biology, Department of Biological Sciences, Imperial College London, South Kensington Campus, London, UK
    EMBO J 23:1030-9. 2004
    The AAA ATPase p97/VCP is involved in many cellular events including ubiquitin-dependent processes and membrane fusion. In the latter, the p97 adaptor protein p47 is of central importance...
  14. pmc The homozygote VCP(R¹⁵⁵H/R¹⁵⁵H) mouse model exhibits accelerated human VCP-associated disease pathology
    Angele Nalbandian
    Department of Pediatrics, University of California Irvine, Irvine, California, United States of America
    PLoS ONE 7:e46308. 2012
    Valosin containing protein (VCP) mutations are the cause of hereditary inclusion body myopathy, Paget's disease of bone, frontotemporal dementia (IBMPFD)...
  15. 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
    Mutations in valosin-containing protein (VCP) cause inclusion body myopathy (IBM), Paget's disease of the bone, and frontotemporal dementia (IBMPFD)...
  16. 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 ..
  17. pmc Reversible inhibitor of p97, DBeQ, impairs both ubiquitin-dependent and autophagic protein clearance pathways
    Tsui Fen Chou
    Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Proc Natl Acad Sci U S A 108:4834-9. 2011
    A specific small-molecule inhibitor of p97 would provide an important tool to investigate diverse functions of this essential ATPase associated with diverse cellular activities (AAA) ATPase and to evaluate its potential to be a ..
  18. doi Transgenic mice expressing mutant forms VCP/p97 recapitulate the full spectrum of IBMPFD including degeneration in muscle, brain and bone
    Sara K Custer
    Department of Developmental Neurobiology, St Jude Children s Research, Hospital, Memphis, TN 38105, USA
    Hum Mol Genet 19:1741-55. 2010
    ..VCP (p97 in mouse, TER94 in Drosophila melanogaster and CDC48 in Saccharomyces cerevisiae) is a highly conserved AAA(+)-ATPase that regulates a wide array of cellular processes...
  19. pmc A complex of mammalian ufd1 and npl4 links the AAA-ATPase, p97, to ubiquitin and nuclear transport pathways
    H H Meyer
    Department of Cell Biology, Yale University School of Medicine, 333 Cedar Street, SHM, C441, PO Box 208002, New Haven, CT 06520 8002, USA
    EMBO J 19:2181-92. 2000
    The AAA-ATPase, p97/Cdc48p, has been implicated in many different pathways ranging from membrane fusion to ubiquitin-dependent protein degradation...
  20. 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 ..
  21. pmc Function of the p97-Ufd1-Npl4 complex in retrotranslocation from the ER to the cytosol: dual recognition of nonubiquitinated polypeptide segments and polyubiquitin chains
    Yihong Ye
    Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    J Cell Biol 162:71-84. 2003
    A member of the family of ATPases associated with diverse cellular activities, called p97 in mammals and Cdc48 in yeast, associates with the cofactor Ufd1-Npl4 to move polyubiquitinated polypeptides from the endoplasmic reticulum (ER) ..
  22. ncbi The AAA ATPase Cdc48/p97 and its partners transport proteins from the ER into the cytosol
    Y Ye
    Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 414:652-6. 2001
    ..Here we demonstrate that another member of this family, Cdc48 in yeast and p97 in mammals, is required for the export of ER proteins into the cytosol...
  23. pmc AAA-ATPase p97/Cdc48p, a cytosolic chaperone required for endoplasmic reticulum-associated protein degradation
    Efrat Rabinovich
    Department of Biochemistry, George S Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel
    Mol Cell Biol 22:626-34. 2002
    ..as well as soluble lumenal CPY*, two short-lived ERAD substrates, are markedly stabilized in conditional cdc48 yeast mutants...
  24. 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 ..
  25. pmc Direct binding of ubiquitin conjugates by the mammalian p97 adaptor complexes, p47 and Ufd1-Npl4
    Hemmo H Meyer
    Department of Cell Biology, Yale University School of Medicine, 333 Cedar Street, SHM, C441, PO Box 208002, New Haven, CT 06520 8002, USA
    EMBO J 21:5645-52. 2002
    The multiple functions of the p97/Cdc48p ATPase can be explained largely by adaptors that link its activity to different cellular pathways, but how these adaptors recognize different substrates is unclear...
  26. ncbi Characterization of the mouse gene for the U-box-type ubiquitin ligase UFD2a
    Chie Kaneko
    Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka, Fukuoka, 812 8582, Japan
    Biochem Biophys Res Commun 300:297-304. 2003
    ..We also show that UFD2a interacts with VCP (a AAA-family ATPase) that is thought to mediate protein folding...
  27. 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
    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...
  28. ncbi The crystal structure of murine p97/VCP at 3.6A
    Trevor Huyton
    Department of Biological Sciences, Imperial College London, South Kensington SW7 2AZ, UK
    J Struct Biol 144:337-48. 2003
    p97/VCP is a member of the AAA ATPase family and has roles in both membrane fusion and ubiquitin dependent protein degradation. Here, we present a 3...
  29. ncbi Structure of the AAA ATPase p97
    X Zhang
    Molecular Structure and Function Laboratory, Imperial Cancer Research Fund, London SW7 2AY, United Kingdom
    Mol Cell 6:1473-84. 2000
    b>p97, an abundant hexameric ATPase of the AAA family, is involved in homotypic membrane fusion. It is thought to disassemble SNARE complexes formed during the process of membrane fusion...
  30. ncbi The mouse p97 (CDC48) gene. Genomic structure, definition of transcriptional regulatory sequences, gene expression, and characterization of a pseudogene
    J M Muller
    Cell Biology Laboratory, Imperial Cancer Research Fund, Lincoln s Inn Fields, London WC2A 3PX, UK
    J Biol Chem 274:10154-62. 1999
    ..organization, transcriptional regulatory sequences, and adult and embryonic gene expression for the mouse p97(CDC48) AAA ATPase...
  31. pmc Global gene expression profiling in R155H knock-in murine model of VCP disease
    Angele Nalbandian
    Department of Pediatrics, Division of Genetics and Metabolism, University of California Irvine, Irvine, California, USA
    Clin Transl Sci 8:8-16. 2015
    Dominant mutations in the valosin-containing protein (VCP) gene cause inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia, which is characterized by progressive muscle weakness, dysfunction in bone ..
  32. doi SDF2L1 interacts with the ER-associated degradation machinery and retards the degradation of mutant proinsulin in pancreatic β-cells
    Akansha Tiwari
    Division of Cellular and Molecular Biology, Toronto General Research Institute, University Health Network, ON M5G 1L7, Canada
    J Cell Sci 126:1962-8. 2013
    ..We suggest that SDF2L1 increases the time that misfolded proteins have to achieve a correctly folded conformation and thus that SDF2L1 can act as a buffer for substrate availability for ERAD in pancreatic β-cells...
  33. pmc A stress-responsive system for mitochondrial protein degradation
    Jin Mi Heo
    Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
    Mol Cell 40:465-80. 2010
    We show that Ydr049 (renamed VCP/Cdc48-associated mitochondrial stress-responsive--Vms1), a member of an unstudied pan-eukaryotic protein family, translocates from the cytosol to mitochondria upon mitochondrial stress...
  34. pmc A functional deficiency of TERA/VCP/p97 contributes to impaired DNA repair in multiple polyglutamine diseases
    Kyota Fujita
    Department of Neuropathology, Medical Research Institute, Tokyo Medical and Dental University, 1 5 45, Yushima, Bunkyo ku, Tokyo 113 8510, Japan
    Nat Commun 4:1816. 2013
    ..Here we show that transitional endoplasmic reticulum ATPase (TERA)/valosin-containing protein (VCP)/p97 directly binds to multiple polyglutamine disease ..
  35. pmc The valosin-containing protein promotes cardiac survival through the inducible isoform of nitric oxide synthase
    Paulo Lizano
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, 07103, USA
    Cardiovasc Res 99:685-93. 2013
    ..We tested both in vivo and in vitro the hypothesis that such an effector is the valosin-containing protein (VCP), an Akt substrate, which activates the transcription factor NF-κB, using a transgenic mouse with cardiac-specific ..
  36. doi Mechanism of transient binding and release of substrate protein during the allosteric cycle of the p97 nanomachine
    Sam Tonddast-Navaei
    Department of Chemistry, University of Cincinnati, Cincinnati, Ohio 45221, United States
    J Am Chem Soc 135:14627-36. 2013
    ..The p97 ATPase is a homohexameric, double-ring member of this superfamily that encloses a central channel with nonuniform ..
  37. pmc Exercise training reverses skeletal muscle atrophy in an experimental model of VCP disease
    Angele Nalbandian
    Department of Pediatrics, Division of Genetics and Metabolism, University of California Irvine, Irvine, California, United States of America
    PLoS ONE 8:e76187. 2013
    ..Mutations in the valosin containing protein (VCP) gene lead to Inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD) ..
  38. doi Signal-peptide-mediated translocation is regulated by a p97-AIRAPL complex
    Tal Glinka
    Department of Biochemistry, Rappaport Family Institute for Research in the Medical Sciences, Technion Israel Institute of Technology, Haifa 31096, Israel
    Biochem J 457:253-61. 2014
    ..In the present paper, we report that AIRAPL binds and forms a complex with p97 [VCP (valosin-containing protein)/Cdc48], Ubxd8 (ubiquitin regulatory X domain 8), Npl4-Ufd1, Derlin-1 and Bag6 on the ER (endoplasmic reticulum) membrane...
  39. pmc Enhanced endoplasmic reticulum entry of tumor antigen is crucial for cross-presentation induced by dendritic cell-targeted vaccination
    Hongxia Wang
    Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA 23298
    J Immunol 191:6010-21. 2013
    ..These results also reinforce the importance of the ER-associated protein quality control machinery and the mode of the Ag delivery in regulating DC-elicited immune outcomes. ..
  40. pmc Novel VCP modulators mitigate major pathologies of rd10, a mouse model of retinitis pigmentosa
    Hanako Ohashi Ikeda
    1 Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto 606 8501, Japan 2 Laboratory of Functional Biology, Kyoto University Graduate School of Biostudies, Kyoto 606 8501, Japan
    Sci Rep 4:5970. 2014
    ..describe small compounds (Kyoto University Substances, KUSs) that were developed to inhibit the ATPase activity of VCP (valosin-containing protein), the most abundant soluble ATPase in the cell...
  41. pmc Cytolethal distending toxins require components of the ER-associated degradation pathway for host cell entry
    Aria Eshraghi
    Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, California, United States of America
    PLoS Pathog 10:e1004295. 2014
    ..ER associated degradation (ERAD) machinery, Derlin-2 (Derl2), the E3 ubiquitin-protein ligase Hrd1, and the AAA ATPase p97, are required for intoxication by some CDTs...
  42. pmc Degradation of the deubiquitinating enzyme USP33 is mediated by p97 and the ubiquitin ligase HERC2
    Nickie C Chan
    From the Division of Biology and Biological Engineering, The Howard Hughes Medical Institute, and
    J Biol Chem 289:19789-98. 2014
    ..mass spectrometry, we found that the intracellular level of USP33 is highly sensitive to the activity of p97. Knockdown or chemical inhibition of p97 causes robust accumulation of USP33 due to inhibition of its degradation...
  43. pmc Pro178 and Pro183 of selenoprotein S are essential residues for interaction with p97(VCP) during endoplasmic reticulum-associated degradation
    Jea Hwang Lee
    From the Laboratory of Cellular and Molecular Biochemistry, Division of Life Sciences, Korea University, 1, 5 Ka, Anam Dong, Sungbuk Ku, Seoul 136 701, Republic of Korea and
    J Biol Chem 289:13758-68. 2014
    During endoplasmic reticulum (ER)-associated degradation, p97(VCP) is recruited to the ER membrane through interactions with transmembrane proteins, such as selenoprotein S (SelS), selenoprotein K (SelK), hrd1, and gp78...
  44. doi Isolation of a point-mutated p47 lacking binding affinity to p97ATPase
    Yayoi Kaneko
    Department of Molecular Cell Biology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
    FEBS Lett 584:3873-7. 2010
    p47, a p97-binding protein, functions in Golgi membrane fusion together with p97 and VCIP135, another p97-binding protein. We have succeeded in creating p47 with a point mutation, F253S, which lacks p97-binding affinity...
  45. pmc Valosin-containing protein regulates the proteasome-mediated degradation of DNA-PKcs in glioma cells
    N Jiang
    Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
    Cell Death Dis 4:e647. 2013
    ..The VCP (valosine-containing protein), a chaperone protein that regulates ubiquitin-dependent protein degradation, is ..
  46. 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...
  47. doi ER-stress-inducible Herp, facilitates the degradation of immature nicastrin
    Toshihiro Marutani
    Department of Biology, Faculty of Sciences, Kyushu University Graduate School, Fukuoka 812 8581, Japan
    Biochim Biophys Acta 1810:790-8. 2011
    ..However, its biological functions are not fully understood. Here, we examined the role of Herp in the degradation of γ-secretase components...
  48. pmc RNF170 protein, an endoplasmic reticulum membrane ubiquitin ligase, mediates inositol 1,4,5-trisphosphate receptor ubiquitination and degradation
    Justine P Lu
    Department of Pharmacology, State University of New York Upstate Medical University, Syracuse, New York 13210, USA
    J Biol Chem 286:24426-33. 2011
    ..Thus, RNF170 plays an essential role in IP(3) receptor processing via the ubiquitin-proteasome pathway...
  49. pmc Valosin-containing protein and neurofibromin interact to regulate dendritic spine density
    Hsiao Fang Wang
    Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan
    J Clin Invest 121:4820-37. 2011
    ..Although it is known to be caused by mutations in the gene encoding valosin-containing protein (VCP), the underlying disease mechanism remains elusive...
  50. pmc A novel conserved isoform of the ubiquitin ligase UFD2a/UBE4B is expressed exclusively in mature striated muscle cells
    ANDREW L MAMMEN
    Johns Hopkins University School of Medicine, Department of Medicine, Division of Rheumatology, Baltimore, Maryland, United States of America
    PLoS ONE 6:e28861. 2011
    ..UFD2a interacts with VCP/p97, an AAA-type ATPase implicated in processes whose functions appear to be regulated, in part, through their ..
  51. 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...
  52. pmc Dynamic flexibility of the ATPase p97 is important for its interprotomer motion transmission
    Chengdong Huang
    Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794 5215, USA
    Proc Natl Acad Sci U S A 109:9792-7. 2012
    The hexameric protein p97, a very abundant type II AAA ATPase (ATPase associated with various cellular activities), is involved in a diverse range of cellular functions...
  53. pmc The p97/VCP ATPase is critical in muscle atrophy and the accelerated degradation of muscle proteins
    Rosanna Piccirillo
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    EMBO J 31:3334-50. 2012
    The p97/VCP ATPase complex facilitates the extraction and degradation of ubiquitinated proteins from larger structures. We therefore studied if p97 participates to the rapid degradation of myofibrillar proteins during muscle atrophy...
  54. pmc Proteomic profiling of a mouse model for ovarian granulosa cell tumor identifies VCP as a highly sensitive serum tumor marker in several human cancers
    Marie Noëlle Laguë
    Centre de Recherche en Reproduction Animale, Faculte de Medecine Veterinaire, Universite de Montreal, Montreal, Quebec, Canada
    PLoS ONE 7:e42470. 2012
    ..by mass spectrometry showed that vinculin, enolase 1, several heat shock proteins, and valosin containing protein (VCP) were more abundantly secreted by cultured mouse GCT cells compared to primary cultured GC...
  55. ncbi Distinct steps in dislocation of luminal endoplasmic reticulum-associated degradation substrates: roles of endoplamic reticulum-bound p97/Cdc48p and proteasome
    Yechiel Elkabetz
    Department of Biochemistry, George S Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel
    J Biol Chem 279:3980-9. 2004
    ..but requires p97/Cdc48p because substrates remain entrapped in ER lumen and are prevented from ubiquitination in cdc48 yeast strain. The second dislocation step is the release of accumulated substrates to the cytosol...
  56. pmc AAA ATPase p97/VCP is essential for TRIM21-mediated virus neutralization
    Felix Hauler
    Protein and Nucleic Acid Chemistry Division, Medical Research Council Laboratory of Molecular Biology, Cambridge, CB2 0QH, United Kingdom
    Proc Natl Acad Sci U S A 109:19733-8. 2012
    ..Here, we identify the ATPase p97/valosin-containing protein (VCP), an enzyme with segregase and unfoldase activity, as a key player in this process...
  57. pmc mTOR dysfunction contributes to vacuolar pathology and weakness in valosin-containing protein associated inclusion body myopathy
    James K Ching
    Department of Neurology, Hope Center for Neurological Diseases, Washington University School of Medicine, St Louis, MO 63110, USA
    Hum Mol Genet 22:1167-79. 2013
    ..Mutations in valosin-containing protein (VCP) cause inclusion body myopathy (IBM) associated with Paget's disease of the bone, fronto-temporal dementia and ..
  58. pmc Bipartite determinants mediate an evolutionarily conserved interaction between Cdc48 and the 20S peptidase
    Dominik Barthelme
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 110:3327-32. 2013
    ..In archaea, 20S can function with the AAA+ Cdc48 or proteasome-activating nucleotidase (PAN) unfoldases...
  59. ncbi Interaction of U-box-type ubiquitin-protein ligases (E3s) with molecular chaperones
    Shigetsugu Hatakeyama
    Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka, Fukuoka 812 8582, Japan
    Genes Cells 9:533-48. 2004
    ..Two representative mammalian U-box proteins, UFD2a and CHIP, interact with the molecular chaperones VCP and either Hsp90 or Hsc70, respectively, and are implicated in the degradation of damaged proteins...
  60. pmc Tau accumulation activates the unfolded protein response by impairing endoplasmic reticulum-associated degradation
    Jose F Abisambra
    Sanders Brown Center on Aging and Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky 40536, USA
    J Neurosci 33:9498-507. 2013
    ..associated proteins that are essential for ER-associated degradation (ERAD), including valosin-containing protein (VCP) and Hrd1...
  61. pmc Mannose receptor polyubiquitination regulates endosomal recruitment of p97 and cytosolic antigen translocation for cross-presentation
    Matthias Zehner
    Life and Medical Sciences Institute, University of Bonn, 53115 Bonn, Germany
    Proc Natl Acad Sci U S A 108:9933-8. 2011
    ..Importantly, we demonstrate that MR polyubiquitination mediates the recruitment of p97, a member of the ER-associated degradation machinery that provides the driving force for antigen translocation, ..
  62. doi Polycystin-2 is regulated by endoplasmic reticulum-associated degradation
    Genqing Liang
    Membrane Protein Research Group, Department of Physiology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada T6G 2H7
    Hum Mol Genet 17:1109-19. 2008
    ..PC2 interacted with ATPase p97, a well-known ERAD component extracting substrates from ER, and immobilized it in perinuclear regions...
  63. pmc The AAA ATPase p97 links peptide N-glycanase to the endoplasmic reticulum-associated E3 ligase autocrine motility factor receptor
    Guangtao Li
    Department of Biochemistry and Cell Biology, 450 Life Sciences Building, Stony Brook University, Stony Brook, NY 11794 5215, USA
    Proc Natl Acad Sci U S A 103:8348-53. 2006
    ....
  64. ncbi Tyrosine phosphorylation of VCP, the mammalian homologue of the Saccharomyces cerevisiae CDC48 protein, is unusually sensitive to stimulation by sodium vanadate and hydrogen peroxide
    R J Schulte
    Molecular Biology and Virology Laboratory, Salk Institute, San Diego, CA 92186
    J Immunol 153:5465-72. 1994
    ..VCP is the mammalian homologue of the Saccharomyces cerevisiae CDC48 protein and has localized regions of sequence identity with the yeast Sec18 and Pas1 proteins and the mammalian ..
  65. ncbi Mapping the valosin-containing protein (VCP) gene on human chromosome 9 and mouse chromosome 4, and a likely pseudogene on the mouse X chromosome
    J Hoyle
    Neurogenetics Unit, Imperial College of Medicine at St Mary s, London, UK
    Mamm Genome 8:778-80. 1997
  66. 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 (ubiquitin ..
  67. 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...
  68. ncbi Molecular components of a cell death pathway activated by endoplasmic reticulum stress
    Rammohan V Rao
    The Buck Institute for Age Research, Novato, California 94945, USA
    J Biol Chem 279:177-87. 2004
    ..Our data identify two molecules, valosin-containing protein and apoptosis-linked gene-2 (ALG-2), that appear to play a role in mediating ER stress-induced cell death...
  69. ncbi Quantification of synapse formation and maintenance in vivo in the absence of synaptic release
    J Bouwman
    Rudolf Magnus Institute for Neurosciences, University of Utrecht Medical Center, Utrecht, The Netherlands
    Neuroscience 126:115-26. 2004
    ..These two observations suggest that secretion of neurotransmitters and neuromodulatory substances is required for synapse maintenance, not for synaptogenesis. Multivesicular structures may develop out of unstable synapses...
  70. 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...
  71. pmc Glycoprotein-specific ubiquitin ligases recognize N-glycans in unfolded substrates
    Yukiko Yoshida
    Tokyo Metropolitan Institute of Medical Science, 3 18 22, Hon komagome, Bunkyo ku, Tokyo 113 8613, Japan
    EMBO Rep 6:239-44. 2005
    ..The SCF(Fbs1) complex was associated with p97/VCP AAA ATPase and bound to integrin-beta1, one of the SCF(Fbs1) substrates, in the cytosol in a manner dependent ..
  72. ncbi Identification and characterization of valosin-containing protein (VCP/p97) in untransformed osteoblast-like cells
    Keyvan Behnam
    Department of Physiological Sciences, University of California, Los Angeles, 90024, USA
    J Orthop Res 23:618-24. 2005
    A 97-kDa protein called valosin-containing protein (VCP) has been implicated in osteosarcoma metastasis and Paget's disease of bone, two conditions that complicate the course and outcome of orthopaedic surgery...
  73. pmc Involvement of the p97-Ufd1-Npl4 complex in the regulated endoplasmic reticulum-associated degradation of inositol 1,4,5-trisphosphate receptors
    Kamil J Alzayady
    Departments of Pharmacology and Medicine, SUNY Upstate Medical University, Syracuse, New York 13210 2339, USA
    J Biol Chem 280:34530-7. 2005
    ..Here, we examine this process and show in several mammalian cell types that the ATPase p97 associates with IP(3) receptors in response to hormonal stimuli that induce IP(3) receptor ubiquitination...
  74. pmc Multiple modes of interaction of the deglycosylation enzyme, mouse peptide N-glycanase, with the proteasome
    Guangtao Li
    Department of Biochemistry and Cell Biology, State University of New York, Stony Brook, NY 11794 5215, USA
    Proc Natl Acad Sci U S A 102:15809-14. 2005
    ..Surprisingly, mPNGase also was found to mediate binding of the cytoplasmic protein, p97, to the proteasome through the formation of a ternary complex made up of mHR23B, mPNGase, and p97...
  75. pmc The slow Wallerian degeneration protein, WldS, binds directly to VCP/p97 and partially redistributes it within the nucleus
    Heike Laser
    Institute for Genetics and Center for Molecular Medicine, University of Cologne, D 50674 Cologne, Germany
    Mol Biol Cell 17:1075-84. 2006
    ..We report direct binding of N70 to valosin-containing protein (VCP; p97/Cdc48), a protein with diverse cellular roles including a pivotal role in the ubiquitin proteasome system...
  76. pmc VCP associated inclusion body myopathy and paget disease of bone knock-in mouse model exhibits tissue pathology typical of human disease
    Mallikarjun Badadani
    Department of Pediatrics, University of California Irvine, Irvine, California, United States of America
    PLoS ONE 5:. 2010
    Dominant mutations in the valosin containing protein (VCP) gene cause inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD)...
  77. ncbi Detailed structural insights into the p97-Npl4-Ufd1 interface
    Rivka L Isaacson
    Division of Molecular Biosciences, Imperial College London, Biochemistry Building, South Kensington, London SW7 2AZ, United Kingdom
    J Biol Chem 282:21361-9. 2007
    The AAA ATPase, p97, achieves its versatility through binding to a wide range of cofactor proteins that adapt it to different cellular functions...
  78. pmc Studies on peptide:N-glycanase-p97 interaction suggest that p97 phosphorylation modulates endoplasmic reticulum-associated degradation
    Gang Zhao
    Center for Structural Biology, Deparatment of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794 5115, USA
    Proc Natl Acad Sci U S A 104:8785-90. 2007
    During endoplasmic reticulum-associated degradation, the multifunctional AAA ATPase p97 is part of a protein degradation complex. p97 associates via its N-terminal domain with various cofactors to recruit ubiquitinated substrates...
  79. pmc HDAC6 controls major cell response pathways to cytotoxic accumulation of protein aggregates
    Cyril Boyault
    Institut National de la Sante et de la Recherche Medicale INSERM, U823, Institut Albert Bonniot, Grenoble F 38706, France
    Genes Dev 21:2172-81. 2007
    ..HDAC6 therefore appears as a master regulator of the cell protective response to cytotoxic protein aggregate formation...
  80. pmc VCP, the mammalian homolog of cdc48, is tyrosine phosphorylated in response to T cell antigen receptor activation
    M Egerton
    Cell Biology and Metabolism Branch, National Institute for Child Health and Human Development, NIH, Bethesda, MD 20892
    EMBO J 11:3533-40. 1992
    ..that the amino acid sequence data showed pp100 to be the murine equivalent of porcine valosin containing protein (VCP), a finding confirmed from the cloning and sequencing of the murine pp100 cDNA...
  81. pmc Analysis of nucleotide binding to P97 reveals the properties of a tandem AAA hexameric ATPase
    Louise C Briggs
    Division of Molecular Biosciences, Imperial College London, South Kensington, London SW7 2AZ, United Kingdom
    J Biol Chem 283:13745-52. 2008
    b>p97, an essential chaperone in endoplasmic reticulum-associated degradation and organelle biogenesis, contains two AAA domains (D1 and D2) and assembles as a stable hexamer...
  82. doi VCP binding influences intracellular distribution of the slow Wallerian degeneration protein, Wld(S)
    Anna L Wilbrey
    The Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK
    Mol Cell Neurosci 38:325-40. 2008
    ..The N-terminal domain (N70), which is essential for axonal protection in vivo, binds valosin-containing protein (VCP) and targets both Wld(S) and VCP to discrete nuclear foci...
  83. doi Tyrosine phosphorylation of ATPase p97 regulates its activity during ERAD
    Guangtao Li
    Department of Biochemistry and Cell Biology, 450 Life Science Building, Stony Brook University, Stony Brook, NY 11794 5215, USA
    Biochem Biophys Res Commun 375:247-51. 2008
    ..Recently, we demonstrated the existence of a higher order complex consisting of the ER bound E3 ligase gp78, p97, PNGase, and HR23B in mammals...
  84. ncbi [p97ATPase-mediated biogenesis of the Golgi, ER and nuclear envelope]
    Ukiko Fujise
    Department of Molecular Biology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan
    Seikagaku 80:632-7. 2008
  85. pmc An Armadillo motif in Ufd3 interacts with Cdc48 and is involved in ubiquitin homeostasis and protein degradation
    Gang Zhao
    Center for Structural Biology and Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794 5215, USA
    Proc Natl Acad Sci U S A 106:16197-202. 2009
    The yeast AAA-ATPase Cdc48 and the ubiquitin fusion degradation (UFD) proteins play important, evolutionarily conserved roles in ubiquitin dependent protein degradation...
  86. pmc COP9 signalosome interacts ATP-dependently with p97/valosin-containing protein (VCP) and controls the ubiquitination status of proteins bound to p97/VCP
    Sevil Cayli
    Unit of Reproductive Biology, Department of Anatomy and Cell Biology, Justus Liebig University, 35385 Giessen, Germany
    J Biol Chem 284:34944-53. 2009
    Ubiquitinated proteins can alternatively be delivered directly to the proteasome or via p97/VCP (valosin-containing protein)...
  87. doi WldS can delay Wallerian degeneration in mice when interaction with valosin-containing protein is weakened
    B Beirowski
    The Babraham Institute, Babraham Research Campus, Laboratory of Molecular Signalling, Cambridge CB22 3AT, UK
    Neuroscience 166:201-11. 2010
    ..Wld(S) location is influenced by binding to valosin-containing protein (VCP), an essential protein for many cellular processes including membrane fusion and endoplasmic reticulum-associated ..
  88. pmc Endotoxin conditioning induces VCP/p97-mediated and inducible nitric-oxide synthase-dependent Tyr284 nitration in protein phosphatase 2A
    Takashi Ohama
    Department of Microbiology, University of Virginia School of Medicine, Center for Cell Signaling, Charlottesville, Virginia 22908, USA
    J Biol Chem 285:8711-8. 2010
    ..form of PP2A by chromatography plus immunoprecipitation and used mass spectrometry to identify VCP/p97 as a novel partner for PP2Ac...
  89. 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...
  90. ncbi Munc18-1 stabilizes syntaxin 1, but is not essential for syntaxin 1 targeting and SNARE complex formation
    Ruud F G Toonen
    Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
    J Neurochem 93:1393-400. 2005
    ....