VCP

Summary

Gene Symbol: VCP
Description: valosin containing protein
Alias: CDC48, TERA, p97, transitional endoplasmic reticulum ATPase, 15S Mg(2+)-ATPase p97 subunit, TER ATPase
Species: human
Products:     VCP

Top Publications

  1. Lavoie C, Chevet E, Roy L, Tonks N, Fazel A, Posner B, et al. Tyrosine phosphorylation of p97 regulates transitional endoplasmic reticulum assembly in vitro. Proc Natl Acad Sci U S A. 2000;97:13637-42 pubmed
    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. Isakov E, Stanhill A. Stalled proteasomes are directly relieved by P97 recruitment. J Biol Chem. 2011;286:30274-83 pubmed publisher
    ..Here we show a new functional complex between the P97 and the proteasome that is assembled in response to proteasomal impairment...
  3. Ye Y, Shibata Y, Kikkert M, van Voorden S, Wiertz E, Rapoport T. Recruitment of the p97 ATPase and ubiquitin ligases to the site of retrotranslocation at the endoplasmic reticulum membrane. Proc Natl Acad Sci U S A. 2005;102:14132-8 pubmed
    ..extraction from the membrane by the p97 ATPase [also called valosin-containing protein (VCP) or, in yeast, Cdc48]...
  4. Ritz D, Vuk M, Kirchner P, Bug M, Schütz S, Hayer A, et al. Endolysosomal sorting of ubiquitylated caveolin-1 is regulated by VCP and UBXD1 and impaired by VCP disease mutations. Nat Cell Biol. 2011;13:1116-23 pubmed publisher
    The AAA-ATPase VCP (also known as p97) cooperates with distinct cofactors to process ubiquitylated proteins in different cellular pathways...
  5. Tresse E, Salomons F, Vesa J, Bott L, Kimonis V, Yao T, et al. VCP/p97 is essential for maturation of ubiquitin-containing autophagosomes and this function is impaired by mutations that cause IBMPFD. Autophagy. 2010;6:217-27 pubmed
    b>VCP (VCP/p97) is a ubiquitously expressed member of the AAA(+)-ATPase family of chaperone-like proteins that regulates numerous cellular processes including chromatin decondensation, homotypic membrane fusion and ubiquitin-dependent ..
  6. Mimnaugh E, Xu W, Vos M, Yuan X, Neckers L. Endoplasmic reticulum vacuolization and valosin-containing protein relocalization result from simultaneous hsp90 inhibition by geldanamycin and proteasome inhibition by velcade. Mol Cancer Res. 2006;4:667-81 pubmed
    ..lumen are cleared by ER--associated protein degradation, a sequential process requiring valosin-containing protein (VCP)-dependent retrotranslocation followed by ubiquitination and proteasomal proteolysis...
  7. Qiu Y, Tomita Y, Zhang B, Nakamichi I, Morii E, Aozasa K. Pre-B-cell leukemia transcription factor 1 regulates expression of valosin-containing protein, a gene involved in cancer growth. Am J Pathol. 2007;170:152-9 pubmed
    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...
  8. Lass A, McConnell E, Fleck K, Palamarchuk A, Wojcik C. Analysis of Npl4 deletion mutants in mammalian cells unravels new Ufd1-interacting motifs and suggests a regulatory role of Npl4 in ERAD. Exp Cell Res. 2008;314:2715-23 pubmed publisher
    Npl4 is a 67 kDa protein forming a stable heterodimer with Ufd1, which in turn binds the ubiquitous p97/VCP ATPase...
  9. Stojkovic T, Hammouda E, Richard P, Lopez de Munain A, Ruiz Martinez J, Camaño P, et al. Clinical outcome in 19 French and Spanish patients with valosin-containing protein myopathy associated with Paget's disease of bone and frontotemporal dementia. Neuromuscul Disord. 2009;19:316-23 pubmed publisher
    ..and genetic findings in 10 families (19 patients) presenting mutations in the valosin-containing protein (VCP). The mean age at onset was 42 years...

More Information

Publications126 found, 100 shown here

  1. Bruderer R, Brasseur C, Meyer H. The AAA ATPase p97/VCP interacts with its alternative co-factors, Ufd1-Npl4 and p47, through a common bipartite binding mechanism. J Biol Chem. 2004;279:49609-16 pubmed
    The AAA ATPase p97/VCP forms complexes with different adapters to fulfill distinct cellular functions...
  2. Tang W, Li D, Li C, Esser L, Dai R, Guo L, et al. A novel ATP-dependent conformation in p97 N-D1 fragment revealed by crystal structures of disease-related mutants. EMBO J. 2010;29:2217-29 pubmed publisher
    Mutations in p97, a major cytosolic AAA (ATPases associated with a variety of cellular activities) chaperone, cause inclusion body myopathy associated with Paget's disease of the bone and frontotemporal dementia (IBMPFD)...
  3. Ishikawa H, Yasui K, Oketa Y, Suzuki M, Ono S. Increased expression of valosin-containing protein in the skin of patients with amyotrophic lateral sclerosis. J Clin Neurosci. 2012;19:522-6 pubmed publisher
    Valosin-containing protein (VCP) may have a pivotal role in ubiquitin-dependent protein degradation and is implicated in the pathogenesis of neurodegenerative diseases...
  4. Wang Q, Liu Y, Soetandyo N, Baek K, HEGDE R, Ye Y. A ubiquitin ligase-associated chaperone holdase maintains polypeptides in soluble states for proteasome degradation. Mol Cell. 2011;42:758-70 pubmed publisher
    ..degradation (ERAD) employs membrane-bound ubiquitin ligases and the translocation-driving ATPase p97 to retrotranslocate misfolded proteins for proteasomal degradation...
  5. Kimonis V, Kovach M, Waggoner B, Leal S, Salam A, Rimer L, et al. Clinical and molecular studies in a unique family with autosomal dominant limb-girdle muscular dystrophy and Paget disease of bone. Genet Med. 2000;2:232-41 pubmed
    ..Linkage analysis excluded autosomal dominant and recessive LGMD, PDB, and cardiomyopathy loci. Autosomal dominant LGMD associated with PDB is an unusual disorder. Linkage analysis indicates a unique locus in this family. ..
  6. Qiu Y, Morii E, Tomita Y, Zhang B, Matsumura A, Kitaichi M, et al. Prognostic significance of pre B cell leukemia transcription factor 2 (PBX2) expression in non-small cell lung carcinoma. Cancer Sci. 2009;100:1198-209 pubmed publisher
    ..the pre B cell leukemia transcription factor 1 (PBX1) was a transcription factor for valosin-containing protein (VCP), which is involved in invasion and metastasis of cancers...
  7. Bartolomé F, Wu H, Burchell V, Preza E, Wray S, Mahoney C, et al. Pathogenic VCP mutations induce mitochondrial uncoupling and reduced ATP levels. Neuron. 2013;78:57-64 pubmed publisher
    Valosin-containing protein (VCP) is a highly expressed member of the type II AAA+ ATPase family...
  8. Vandermoere F, El Yazidi Belkoura I, Slomianny C, Demont Y, Bidaux G, Adriaenssens E, et al. The valosin-containing protein (VCP) is a target of Akt signaling required for cell survival. J Biol Chem. 2006;281:14307-13 pubmed
    ..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 ..
  9. Zhong X, Pittman R. Ataxin-3 binds VCP/p97 and regulates retrotranslocation of ERAD substrates. Hum Mol Genet. 2006;15:2409-20 pubmed
    ..AT3 binds VCP/p97, a key protein responsible for extracting ERAD substrates from the ER; binding is modulated by the size of the ..
  10. Radhakrishnan S, den Besten W, Deshaies R. p97-dependent retrotranslocation and proteolytic processing govern formation of active Nrf1 upon proteasome inhibition. elife. 2014;3:e01856 pubmed publisher
    ..but is rapidly and efficiently retrotranslocated to the cytosolic side of the membrane in a manner that depends on p97/VCP. Normally, retrotranslocated Nrf1 is degraded promptly by the proteasome and active species do not accumulate...
  11. Dai R, Li C. Valosin-containing protein is a multi-ubiquitin chain-targeting factor required in ubiquitin-proteasome degradation. Nat Cell Biol. 2001;3:740-4 pubmed
    ..We have shown previously that valosin-containing protein (VCP) physically and functionally targets the ubiquitinated nuclear factor kappaB inhibitor, IkappaBalpha to the ..
  12. Madsen L, Kriegenburg F, Vala A, Best D, Prag S, Hofmann K, et al. The tissue-specific Rep8/UBXD6 tethers p97 to the endoplasmic reticulum membrane for degradation of misfolded proteins. PLoS ONE. 2011;6:e25061 pubmed publisher
    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...
  13. Shi Z, Hayashi Y, Mitsuhashi S, Goto K, Kaneda D, Choi Y, et al. Characterization of the Asian myopathy patients with VCP mutations. Eur J Neurol. 2012;19:501-9 pubmed publisher
    Mutations in the valosin-containing protein (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)...
  14. Blount J, Burr A, Denuc A, Marfany G, Todi S. Ubiquitin-specific protease 25 functions in Endoplasmic Reticulum-associated degradation. PLoS ONE. 2012;7:e36542 pubmed publisher
    ..Our data support a model where USP25 counteracts ubiquitination of ERAD substrates by the ubiquitin ligase HRD1, rescuing them from degradation by the proteasome. ..
  15. Reina C, Zhong X, Pittman R. Proteotoxic stress increases nuclear localization of ataxin-3. Hum Mol Genet. 2010;19:235-49 pubmed publisher
    ..Observations in this study provide new and important insights for understanding SCA3 pathology as the nucleus is likely a key site for early pathogenesis. ..
  16. Schulze A, Standera S, Buerger E, Kikkert M, van Voorden S, Wiertz E, et al. The ubiquitin-domain protein HERP forms a complex with components of the endoplasmic reticulum associated degradation pathway. J Mol Biol. 2005;354:1021-7 pubmed
    ..ubiquitin domain protein (UDP) HERP, the ubiquitin protein ligase HRD1, as well as the retro-translocation factors p97, Derlin-1 and VIMP...
  17. Rothballer A, Tzvetkov N, Zwickl P. Mutations in p97/VCP induce unfolding activity. FEBS Lett. 2007;581:1197-201 pubmed
    ..In contrast, none of the members of the eukaryotic p97/VCP protein family has an aromatic residue in the D1 pore...
  18. Böhm S, Lamberti G, Fernández Sáiz V, Stapf C, Buchberger A. Cellular functions of Ufd2 and Ufd3 in proteasomal protein degradation depend on Cdc48 binding. Mol Cell Biol. 2011;31:1528-39 pubmed publisher
    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...
  19. Rabouille C, Kondo H, Newman R, Hui N, Freemont P, Warren G. Syntaxin 5 is a common component of the NSF- and p97-mediated reassembly pathways of Golgi cisternae from mitotic Golgi fragments in vitro. Cell. 1998;92:603-10 pubmed
    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...
  20. Allen M, Buchberger A, Bycroft M. The PUB domain functions as a p97 binding module in human peptide N-glycanase. J Biol Chem. 2006;281:25502-8 pubmed
    The AAA ATPase p97 is a ubiquitin-selective molecular machine involved in multiple cellular processes, including protein degradation through the ubiquitin-proteasome system and homotypic membrane fusion...
  21. Doss Pepe E, Stenroos E, Johnson W, Madura K. 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. Mol Cell Biol. 2003;23:6469-83 pubmed
    ..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 ..
  22. Ballar P, Shen Y, Yang H, Fang S. The role of a novel p97/valosin-containing protein-interacting motif of gp78 in endoplasmic reticulum-associated degradation. J Biol Chem. 2006;281:35359-68 pubmed
    ..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...
  23. Ye Y, Shibata Y, Yun C, Ron D, Rapoport T. A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol. Nature. 2004;429:841-7 pubmed
    ..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...
  24. Pleasure I, Black M, Keen J. Valosin-containing protein, VCP, is a ubiquitous clathrin-binding protein. Nature. 1993;365:459-62 pubmed
    ..The 100K protein has been identified as valosin-containing protein (VCP; ref. 1), an early substrate for tyrosine phosphorylation on T-cell receptor activation...
  25. Grelle G, Kostka S, Otto A, Kersten B, Genser K, Müller E, et al. Identification of VCP/p97, carboxyl terminus of Hsp70-interacting protein (CHIP), and amphiphysin II interaction partners using membrane-based human proteome arrays. Mol Cell Proteomics. 2006;5:234-44 pubmed
  26. Pearce M, Wormer D, Wilkens S, Wojcikiewicz R. An endoplasmic reticulum (ER) membrane complex composed of SPFH1 and SPFH2 mediates the ER-associated degradation of inositol 1,4,5-trisphosphate receptors. J Biol Chem. 2009;284:10433-45 pubmed publisher
    ..We propose that this novel SPFH1/2 complex is a recognition factor that targets IP(3)Rs and perhaps other substrates for ERAD. ..
  27. Qiu L, Pashkova N, Walker J, Winistorfer S, Allali Hassani A, Akutsu M, et al. Structure and function of the PLAA/Ufd3-p97/Cdc48 complex. J Biol Chem. 2010;285:365-72 pubmed publisher
    ..In yeast, loss of Doa1 is suppressed by altering p97/Cdc48 function indicating that physical interaction between PLAA and p97 is functionally important...
  28. Mori F, Tanji K, Toyoshima Y, Sasaki H, Yoshida M, Kakita A, et al. Valosin-containing protein immunoreactivity in tauopathies, synucleinopathies, polyglutamine diseases and intranuclear inclusion body disease. Neuropathology. 2013;33:637-44 pubmed publisher
    Valosin-containing protein (VCP) is associated with multiple cellular functions, including ubiquitin-dependent protein degradation...
  29. Uchiyama K, Jokitalo E, Kano F, Murata M, Zhang X, Canas B, et al. VCIP135, a novel essential factor for p97/p47-mediated membrane fusion, is required for Golgi and ER assembly in vivo. J Cell Biol. 2002;159:855-66 pubmed
    ..a novel essential factor for p97/p47-mediated membrane fusion, named VCIP135 (valosin-containing protein [VCP][p97]/p47 complex-interacting protein, p135), and show that it binds to the p97/p47/syntaxin5 complex and ..
  30. Yamamoto S, Tomita Y, Nakamori S, Hoshida Y, Nagano H, Dono K, et al. Elevated expression of valosin-containing protein (p97) in hepatocellular carcinoma is correlated with increased incidence of tumor recurrence. J Clin Oncol. 2003;21:447-52 pubmed
    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...
  31. Vesa J, Su H, Watts G, Krause S, Walter M, Martin B, et al. Valosin containing protein associated inclusion body myopathy: abnormal vacuolization, autophagy and cell fusion in myoblasts. Neuromuscul Disord. 2009;19:766-72 pubmed publisher
    ..with Paget's disease and frontotemporal dementia (IBMPFD) is caused by mutations in the valosin containing protein (VCP) gene...
  32. Hänzelmann P, Schindelin H. The structural and functional basis of the p97/valosin-containing protein (VCP)-interacting motif (VIM): mutually exclusive binding of cofactors to the N-terminal domain of p97. J Biol Chem. 2011;286:38679-90 pubmed publisher
    ..ATPase associated with various cellular activities) ATPase p97, also referred to as valosin-containing protein (VCP), mediates essential cellular processes, including ubiquitin-dependent protein degradation, and has been linked to ..
  33. Spina S, Van Laar A, Murrell J, Hamilton R, Kofler J, Epperson F, et al. Phenotypic variability in three families with valosin-containing protein mutation. Eur J Neurol. 2013;20:251-8 pubmed publisher
    ..with Paget's disease of the bone and frontotemporal dementia (FTD)] associated with valosin-containing protein (VCP) mutation is described in three families...
  34. Yang H, Li J, Liu S, Zhao J, Jiang Y, Song A, et al. Aggregation of polyglutamine-expanded ataxin-3 sequesters its specific interacting partners into inclusions: implication in a loss-of-function pathology. Sci Rep. 2014;4:6410 pubmed publisher
    ..We found that the aggregates formed by polyQ-expanded Atx3 sequester its interacting partners, such as P97/VCP and ubiquitin conjugates, into the protein inclusions through specific interactions both in vitro and in cells...
  35. Xu Y, Liu Y, Lee J, Ye Y. A ubiquitin-like domain recruits an oligomeric chaperone to a retrotranslocation complex in endoplasmic reticulum-associated degradation. J Biol Chem. 2013;288:18068-76 pubmed publisher
    ..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. ..
  36. Wojcik C, Rowicka M, Kudlicki A, Nowis D, McConnell E, Kujawa M, et al. 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. Mol Biol Cell. 2006;17:4606-18 pubmed
    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)-..
  37. Halawani D, LeBlanc A, Rouiller I, Michnick S, Servant M, Latterich M. 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. Mol Cell Biol. 2009;29:4484-94 pubmed publisher
    ..dementia (hIBMPFTD) is a degenerative disorder caused by single substitutions in highly conserved residues of p97/VCP...
  38. Koike M, Fukushi J, Ichinohe Y, Higashimae N, Fujishiro M, Sasaki C, et al. Valosin-containing protein (VCP) in novel feedback machinery between abnormal protein accumulation and transcriptional suppression. J Biol Chem. 2010;285:21736-49 pubmed publisher
    ..Genetic and biochemical analyses indicate that valosin-containing protein (VCP) is a crucial molecule in the pathogenesis of human neurodegenerative disorders...
  39. Orme C, Bogan J. The ubiquitin regulatory X (UBX) domain-containing protein TUG regulates the p97 ATPase and resides at the endoplasmic reticulum-golgi intermediate compartment. J Biol Chem. 2012;287:6679-92 pubmed publisher
    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...
  40. Soetandyo N, Ye Y. The p97 ATPase dislocates MHC class I heavy chain in US2-expressing cells via a Ufd1-Npl4-independent mechanism. J Biol Chem. 2010;285:32352-9 pubmed publisher
    ..The retrotranslocation also involves the p97 ATPase...
  41. Asai T, Tomita Y, Nakatsuka S, Hoshida Y, Myoui A, Yoshikawa H, et al. VCP (p97) regulates NFkappaB signaling pathway, which is important for metastasis of osteosarcoma cell line. Jpn J Cancer Res. 2002;93:296-304 pubmed
    ..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 ..
  42. Ballar P, Zhong Y, Nagahama M, Tagaya M, Shen Y, Fang S. Identification of SVIP as an endogenous inhibitor of endoplasmic reticulum-associated degradation. J Biol Chem. 2007;282:33908-14 pubmed
    ..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 ..
  43. Madsen L, Andersen K, Prag S, Moos T, Semple C, Seeger M, et al. Ubxd1 is a novel co-factor of the human p97 ATPase. Int J Biochem Cell Biol. 2008;40:2927-42 pubmed publisher
    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 ..
  44. Acs K, Luijsterburg M, Ackermann L, Salomons F, Hoppe T, Dantuma N. The AAA-ATPase VCP/p97 promotes 53BP1 recruitment by removing L3MBTL1 from DNA double-strand breaks. Nat Struct Mol Biol. 2011;18:1345-50 pubmed publisher
    ..ubiquitylation facilitates the recruitment of the AAA-ATPase valosin-containing protein (VCP, also known as p97) and its cofactor NPL4 to sites of double-strand breaks...
  45. Meyer H, Bug M, Bremer S. Emerging functions of the VCP/p97 AAA-ATPase in the ubiquitin system. Nat Cell Biol. 2012;14:117-23 pubmed publisher
    The ATP-driven chaperone valosin-containing protein (VCP)/p97 governs critical steps in ubiquitin-dependent protein quality control and intracellular signalling pathways...
  46. Seigneurin Berny D, Verdel A, Curtet S, Lemercier C, Garin J, Rousseaux S, et al. Identification of components of the murine histone deacetylase 6 complex: link between acetylation and ubiquitination signaling pathways. Mol Cell Biol. 2001;21:8035-44 pubmed
    ..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 ..
  47. Kobayashi T, Tanaka K, Inoue K, Kakizuka A. Functional ATPase activity of p97/valosin-containing protein (VCP) is required for the quality control of endoplasmic reticulum in neuronally differentiated mammalian PC12 cells. J Biol Chem. 2002;277:47358-65 pubmed
    ..We previously identified p97/valosin-containing protein (VCP), an AAA ATPase with two conserved ATPase domains (D1 and D2), as an interacting ..
  48. Wang Q, Li L, Ye Y. Inhibition of p97-dependent protein degradation by Eeyarestatin I. J Biol Chem. 2008;283:7445-54 pubmed publisher
    ..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...
  49. Li G, Zhao G, Schindelin H, Lennarz W. Tyrosine phosphorylation of ATPase p97 regulates its activity during ERAD. Biochem Biophys Res Commun. 2008;375:247-51 pubmed publisher
    ..Recently, we demonstrated the existence of a higher order complex consisting of the ER bound E3 ligase gp78, p97, PNGase, and HR23B in mammals...
  50. Guo Y, Chen J, Shi L, Fan Z. Valosin-containing protein cleavage by granzyme K accelerates an endoplasmic reticulum stress leading to caspase-independent cytotoxicity of target tumor cells. J Immunol. 2010;185:5348-59 pubmed publisher
    ..In this study, we found the valosin-containing protein (VCP) is a physiological substrate of GzmK...
  51. Livingstone M, Ruan H, Weiner J, Clauser K, Strack P, Jin S, et al. Valosin-containing protein phosphorylation at Ser784 in response to DNA damage. Cancer Res. 2005;65:7533-40 pubmed
    ..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...
  52. Haubenberger D, Bittner R, Rauch Shorny S, Zimprich F, Mannhalter C, Wagner L, et al. Inclusion body myopathy and Paget disease is linked to a novel mutation in the VCP gene. Neurology. 2005;65:1304-5 pubmed
    Mutations in the valosin-containing protein (VCP) on chromosome 9p13-p12 were recently found to be associated with hereditary inclusion body myopathy, Paget disease of the bone, and frontotemporal dementia (IBMPFD)...
  53. Alexandru G, Graumann J, Smith G, Kolawa N, Fang R, Deshaies R. UBXD7 binds multiple ubiquitin ligases and implicates p97 in HIF1alpha turnover. Cell. 2008;134:804-16 pubmed publisher
    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...
  54. Griciuc A, Aron L, Piccoli G, Ueffing M. Clearance of Rhodopsin(P23H) aggregates requires the ERAD effector VCP. Biochim Biophys Acta. 2010;1803:424-34 pubmed publisher
    ..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 ..
  55. Li G, Huang C, Zhao G, Lennarz W. Interprotomer motion-transmission mechanism for the hexameric AAA ATPase p97. Proc Natl Acad Sci U S A. 2012;109:3737-41 pubmed publisher
    ..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...
  56. Buchan J, Kolaitis R, Taylor J, Parker R. Eukaryotic stress granules are cleared by autophagy and Cdc48/VCP function. Cell. 2013;153:1461-74 pubmed publisher
    ..Analyses of such mutants, including CDC48 alleles, provide evidence that stress granules can be targeted to the vacuole by autophagy, in a process termed ..
  57. Mayr P, Allan V, Woodman P. Phosphorylation of p97(VCP) and p47 in vitro by p34cdc2 kinase. Eur J Cell Biol. 1999;78:224-32 pubmed
    The hexameric ATPase p97/yeast Cdc48p has been implicated in a number of cellular events that are regulated during mitosis, including homotypic membrane fusion, spindle pole body function, and ubiquitin-dependent protein degradation...
  58. Zhang S, Liu J, Kobayashi R, Tonks N. Identification of the cell cycle regulator VCP (p97/CDC48) as a substrate of the band 4.1-related protein-tyrosine phosphatase PTPH1. J Biol Chem. 1999;274:17806-12 pubmed
    ..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...
  59. Ishigaki S, Hishikawa N, Niwa J, Iemura S, Natsume T, Hori S, et al. Physical and functional interaction between Dorfin and Valosin-containing protein that are colocalized in ubiquitylated inclusions in neurodegenerative disorders. J Biol Chem. 2004;279:51376-85 pubmed
    ..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...
  60. Lilley B, Ploegh H. Multiprotein complexes that link dislocation, ubiquitination, and extraction of misfolded proteins from the endoplasmic reticulum membrane. Proc Natl Acad Sci U S A. 2005;102:14296-301 pubmed
    ..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 ..
  61. Forman M, Mackenzie I, Cairns N, Swanson E, Boyer P, Drachman D, et al. Novel ubiquitin neuropathology in frontotemporal dementia with valosin-containing protein gene mutations. J Neuropathol Exp Neurol. 2006;65:571-81 pubmed
    ..of bone (IBMPFD) is a rare, autosomal-dominant disorder caused by mutations in the valosin-containing protein (VCP) gene, a member of the AAA-ATPase gene superfamily...
  62. Younger J, Chen L, Ren H, Rosser M, Turnbull E, Fan C, et al. Sequential quality-control checkpoints triage misfolded cystic fibrosis transmembrane conductance regulator. Cell. 2006;126:571-82 pubmed
    ..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. ..
  63. Morreale G, Conforti L, Coadwell J, Wilbrey A, Coleman M. Evolutionary divergence of valosin-containing protein/cell division cycle protein 48 binding interactions among endoplasmic reticulum-associated degradation proteins. FEBS J. 2009;276:1208-20 pubmed publisher
    ..For example, valosin-containing protein (VCP) and its yeast homologue cell division cycle protein 48 (Cdc48p), which help to direct polyubiquitinated proteins ..
  64. Ju J, Fuentealba R, Miller S, Jackson E, Piwnica Worms D, Baloh R, et al. Valosin-containing protein (VCP) is required for autophagy and is disrupted in VCP disease. J Cell Biol. 2009;187:875-88 pubmed publisher
    Mutations in valosin-containing protein (VCP) cause inclusion body myopathy (IBM), Paget's disease of the bone, and frontotemporal dementia (IBMPFD)...
  65. Fernández Sáiz V, Buchberger A. Imbalances in p97 co-factor interactions in human proteinopathy. EMBO Rep. 2010;11:479-85 pubmed publisher
    The ubiquitin-selective chaperone p97 is involved in major proteolytic pathways of eukaryotic cells and has been implicated in several human proteinopathies...
  66. LaLonde D, Bretscher A. The UBX protein SAKS1 negatively regulates endoplasmic reticulum-associated degradation and p97-dependent degradation. J Biol Chem. 2011;286:4892-901 pubmed publisher
    ..The ATPase p97 acts as an essential component of this process by providing the force needed for retrotranslocation and by serving ..
  67. Chapman E, Fry A, Kang M. The complexities of p97 function in health and disease. Mol Biosyst. 2011;7:700-10 pubmed publisher
    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...
  68. Greenblatt E, Olzmann J, Kopito R. Derlin-1 is a rhomboid pseudoprotease required for the dislocation of mutant ?-1 antitrypsin from the endoplasmic reticulum. Nat Struct Mol Biol. 2011;18:1147-52 pubmed publisher
    ..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...
  69. Niwa H, Ewens C, Tsang C, Yeung H, Zhang X, Freemont P. The role of the N-domain in the ATPase activity of the mammalian AAA ATPase p97/VCP. J Biol Chem. 2012;287:8561-70 pubmed publisher
    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 ..
  70. Rodriguez Ortiz C, Hoshino H, Cheng D, Liu Yescevitz L, Blurton Jones M, Wolozin B, et al. 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. Am J Pathol. 2013;183:504-15 pubmed publisher
    Mutations in valosin-containing protein (VCP) cause a rare, autosomal dominant disease called inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia (IBMPFD)...
  71. Schaeffer V, Akutsu M, Olma M, Gomes L, Kawasaki M, Dikic I. Binding of OTULIN to the PUB domain of HOIP controls NF-?B signaling. Mol Cell. 2014;54:349-61 pubmed publisher
    ..The HOIP PUB domain binds to the PUB interacting motif (PIM) of OTULIN and the chaperone VCP/p97. Structural studies revealed the basis of high-affinity interaction with the OTULIN PIM...
  72. Rabouille C, Levine T, Peters J, Warren G. An NSF-like ATPase, p97, and NSF mediate cisternal regrowth from mitotic Golgi fragments. Cell. 1995;82:905-14 pubmed
    ..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...
  73. Dai R, Chen E, Longo D, Gorbea C, Li C. Involvement of valosin-containing protein, an ATPase Co-purified with IkappaBalpha and 26 S proteasome, in ubiquitin-proteasome-mediated degradation of IkappaBalpha. J Biol Chem. 1998;273:3562-73 pubmed
    ..We identify valosin-containing protein (VCP), an AAA (ATPases associated with a variety of cellular activities) family member, that co-precipitates with ..
  74. Partridge J, Lopreiato J, Latterich M, Indig F. DNA damage modulates nucleolar interaction of the Werner protein with the AAA ATPase p97/VCP. Mol Biol Cell. 2003;14:4221-9 pubmed
    We report a novel nucleolar interaction between the AAA ATPase p97/VCP and the Werner protein (WRNp), a member of the RecQ helicase family...
  75. Yamamoto S, Tomita Y, Hoshida Y, Sakon M, Kameyama M, Imaoka S, et al. Expression of valosin-containing protein in colorectal carcinomas as a predictor for disease recurrence and prognosis. Clin Cancer Res. 2004;10:651-7 pubmed
    Valosin-containing protein (VCP or p97) is associated with antiapoptotic function and metastasis via activation of the nuclear factor-kappaB signaling pathway...
  76. Watts G, Wymer J, Kovach M, Mehta S, Mumm S, Darvish D, et al. Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein. Nat Genet. 2004;36:377-81 pubmed
    ..We found six missense mutations in the gene encoding valosin-containing protein (VCP, a member of the AAA-ATPase superfamily) exclusively in all 61 affected individuals...
  77. Yamamoto S, Tomita Y, Nakamori S, Hoshida Y, Iizuka N, Okami J, et al. Valosin-containing protein (p97) and Ki-67 expression is a useful marker in detecting malignant behavior of pancreatic endocrine neoplasms. Oncology. 2004;66:468-75 pubmed
    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...
  78. Chen B, Mariano J, Tsai Y, Chan A, Cohen M, Weissman A. The activity of a human endoplasmic reticulum-associated degradation E3, gp78, requires its Cue domain, RING finger, and an E2-binding site. Proc Natl Acad Sci U S A. 2006;103:341-6 pubmed
    ..These results also provide proof of principle that interrupting a specific E2-E3 interaction can selectively inhibit ERAD. ..
  79. Boeddrich A, Gaumer S, Haacke A, Tzvetkov N, Albrecht M, Evert B, et al. An arginine/lysine-rich motif is crucial for VCP/p97-mediated modulation of ataxin-3 fibrillogenesis. EMBO J. 2006;25:1547-58 pubmed
    ..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-..
  80. Guinto J, Ritson G, Taylor J, Forman M. Valosin-containing protein and the pathogenesis of frontotemporal dementia associated with inclusion body myopathy. Acta Neuropathol. 2007;114:55-61 pubmed
    ..of bone (IBMPFD) is a rare, autosomal dominant disorder caused by mutations in the gene valosin-containing protein (VCP)...
  81. Watts G, Thomasova D, Ramdeen S, Fulchiero E, Mehta S, Drachman D, et al. Novel VCP mutations in inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia. Clin Genet. 2007;72:420-6 pubmed
    ..IBMPFD, OMIM 167320) has recently been attributed to eight missense mutations in valosin-containing protein (VCP)...
  82. Djamshidian A, Schaefer J, Haubenberger D, Stogmann E, Zimprich F, Auff E, et al. A novel mutation in the VCP gene (G157R) in a German family with inclusion-body myopathy with Paget disease of bone and frontotemporal dementia. Muscle Nerve. 2009;39:389-91 pubmed publisher
    Mutations in the valosin-containing protein (VCP) are known to cause autosomal-dominant inclusion-body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD)...
  83. Gitcho M, Strider J, Carter D, Taylor Reinwald L, Forman M, Goate A, et al. VCP mutations causing frontotemporal lobar degeneration disrupt localization of TDP-43 and induce cell death. J Biol Chem. 2009;284:12384-98 pubmed publisher
    ..inclusion body myopathy and Paget disease of bone is a rare, autosomal dominant disorder caused by mutations in the VCP (valosin-containing protein) gene...
  84. Ernst R, Mueller B, Ploegh H, Schlieker C. The otubain YOD1 is a deubiquitinating enzyme that associates with p97 to facilitate protein dislocation from the ER. Mol Cell. 2009;36:28-38 pubmed publisher
    ..YOD1 is a constituent of a multiprotein complex with p97 as its nucleus, suggesting a functional link to a pathway responsible for the dislocation of misfolded proteins ..
  85. Kumar K, Needham M, Mina K, Davis M, Brewer J, Staples C, et al. Two Australian families with inclusion-body myopathy, Paget's disease of bone and frontotemporal dementia: novel clinical and genetic findings. Neuromuscul Disord. 2010;20:330-4 pubmed publisher
    ..A novel mutation in the valosin-containing protein (VCP) gene (p.Arg155Leu) was found in one family while the other family had a previously reported mutation (p.Leu198Trp)...
  86. Johnson J, Mandrioli J, Benatar M, Abramzon Y, Van Deerlin V, Trojanowski J, et al. Exome sequencing reveals VCP mutations as a cause of familial ALS. Neuron. 2010;68:857-64 pubmed publisher
    Using exome sequencing, we identified a p.R191Q amino acid change in the valosin-containing protein (VCP) gene in an Italian family with autosomal dominantly inherited amyotrophic lateral sclerosis (ALS)...
  87. Tanaka A, Cleland M, Xu S, Narendra D, Suen D, Karbowski M, et al. Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin. J Cell Biol. 2010;191:1367-80 pubmed publisher
    ..fusion, is induced by Parkin upon membrane depolarization and leads to their degradation in a proteasome- and p97-dependent manner...
  88. Olzmann J, Richter C, Kopito R. Spatial regulation of UBXD8 and p97/VCP controls ATGL-mediated lipid droplet turnover. Proc Natl Acad Sci U S A. 2013;110:1345-50 pubmed publisher
    UBXD8 is a membrane-embedded recruitment factor for the p97/VCP segregase that has been previously linked to endoplasmic reticulum (ER)-associated degradation and to the control of triacylglycerol synthesis in the ER...
  89. Kim S, Cho J, Song E, Kim S, Kim H, Lee K, et al. Structural basis for ovarian tumor domain-containing protein 1 (OTU1) binding to p97/valosin-containing protein (VCP). J Biol Chem. 2014;289:12264-74 pubmed publisher
    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...
  90. Zhang H, Wang Q, Kajino K, Greene M. VCP, a weak ATPase involved in multiple cellular events, interacts physically with BRCA1 in the nucleus of living cells. DNA Cell Biol. 2000;19:253-63 pubmed
    ..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...
  91. Nagahama M, Suzuki M, Hamada Y, Hatsuzawa K, Tani K, Yamamoto A, et al. SVIP is a novel VCP/p97-interacting protein whose expression causes cell vacuolation. Mol Biol Cell. 2003;14:262-73 pubmed
    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...
  92. Zhong X, Shen Y, Ballar P, Apostolou A, Agami R, Fang S. AAA ATPase p97/valosin-containing protein interacts with gp78, a ubiquitin ligase for endoplasmic reticulum-associated degradation. J Biol Chem. 2004;279:45676-84 pubmed
    ..AAA ATPase (ATPase associated with various cellular activities) p97/valosin-containing protein (VCP) subsequently dislodges the ubiquitinated proteins from the ER and chaperones them ..