CHIP

Summary

Gene Symbol: CHIP
Description: STIP1 homology and U-box containing protein 1
Alias: CHIP, HSPABP2, NY-CO-7, SCAR16, SDCCAG7, UBOX1, E3 ubiquitin-protein ligase CHIP, CLL-associated antigen KW-8, RING-type E3 ubiquitin transferase CHIP, STIP1 homology and U-box containing protein 1, E3 ubiquitin protein ligase, antigen NY-CO-7, carboxy terminus of Hsp70-interacting protein, heat shock protein A binding protein 2 (c-terminal), serologically defined colon cancer antigen 7
Species: human
Products:     CHIP

Top Publications

  1. Fan M, Park A, Nephew K. CHIP (carboxyl terminus of Hsc70-interacting protein) promotes basal and geldanamycin-induced degradation of estrogen receptor-alpha. Mol Endocrinol. 2005;19:2901-14 pubmed
    ..One potential mechanism involves CHIP, the carboxyl terminus of Hsc70-interacting protein, previously shown to target Hsp90-interacting proteins for ..
  2. Dai Q, Zhang C, Wu Y, McDonough H, Whaley R, Godfrey V, et al. CHIP activates HSF1 and confers protection against apoptosis and cellular stress. EMBO J. 2003;22:5446-58 pubmed
    ..We demonstrate that the dual function co-chaperone/ubiquitin ligase CHIP (C-terminus of Hsp70-interacting protein) regulates activation of the stress-chaperone response through induced ..
  3. Morishima Y, Wang A, Yu Z, Pratt W, Osawa Y, Lieberman A. CHIP deletion reveals functional redundancy of E3 ligases in promoting degradation of both signaling proteins and expanded glutamine proteins. Hum Mol Genet. 2008;17:3942-52 pubmed publisher
    b>CHIP (carboxy terminus of Hsc70-interacting protein) an E3 ubiquitin ligase that binds to Hsp70 and Hsp90, promotes degradation of several Hsp90-regulated signaling proteins and disease-causing proteins containing expanded glutamine ..
  4. Sisoula C, Trachana V, Patterson C, Gonos E. CHIP-dependent p53 regulation occurs specifically during cellular senescence. Free Radic Biol Med. 2011;50:157-65 pubmed publisher
    ..However, other E3 ligases have been identified, such as the chaperone-associated ligase CHIP, although their precise function regarding p53 degradation remains elusive...
  5. Sha Y, Pandit L, Zeng S, Eissa N. A critical role for CHIP in the aggresome pathway. Mol Cell Biol. 2009;29:116-28 pubmed publisher
    ..b>CHIP (carboxy terminus of Hsp70-interacting protein) is a highly conserved protein that has been shown to mediate ..
  6. Wang L, Liu Y, Hao R, Chen L, Chang Z, Wang H, et al. Molecular mechanism of the negative regulation of Smad1/5 protein by carboxyl terminus of Hsc70-interacting protein (CHIP). J Biol Chem. 2011;286:15883-94 pubmed publisher
    ..The C terminus of Hsc70-interacting protein (CHIP) serves as an E3 ubiquitin ligase to mediate the degradation of Smad proteins and many other signaling proteins...
  7. Naito A, Okada S, Minamino T, Iwanaga K, Liu M, Sumida T, et al. Promotion of CHIP-mediated p53 degradation protects the heart from ischemic injury. Circ Res. 2010;106:1692-702 pubmed publisher
    ..Through expression screening, we found that CHIP (carboxyl terminus of Hsp70-interacting protein) is an endogenous p53 antagonist in the heart...
  8. Lee J, Seo T, Yi J, Shin K, Yoo S. CHIP has a protective role against oxidative stress-induced cell death through specific regulation of endonuclease G. Cell Death Dis. 2013;4:e666 pubmed publisher
    ..The E3 ligase C terminus of Hsc-70 interacting protein (CHIP) has a protective role against various stresses by targeting damaged proteins for proteasomal degradation, and thus ..
  9. Stankiewicz M, Nikolay R, Rybin V, Mayer M. CHIP participates in protein triage decisions by preferentially ubiquitinating Hsp70-bound substrates. FEBS J. 2010;277:3353-67 pubmed publisher
    The E3 ubiquitin ligase CHIP (C-terminus of Hsc70-interacting protein) is believed to be a central player in the cellular triage decision, as it links the molecular chaperones Hsp70/Hsc70 and Hsp90 to the ubiquitin proteasomal degradation ..

More Information

Publications108 found, 100 shown here

  1. Dolan P, Johnson G. A caspase cleaved form of tau is preferentially degraded through the autophagy pathway. J Biol Chem. 2010;285:21978-87 pubmed publisher
  2. Esser C, Scheffner M, Hohfeld J. The chaperone-associated ubiquitin ligase CHIP is able to target p53 for proteasomal degradation. J Biol Chem. 2005;280:27443-8 pubmed
    ..Here we show that the chaperone-associated ubiquitin ligase CHIP is able to induce the proteasomal degradation of p53...
  3. Paul I, Ahmed S, Bhowmik A, Deb S, Ghosh M. The ubiquitin ligase CHIP regulates c-Myc stability and transcriptional activity. Oncogene. 2013;32:1284-95 pubmed publisher
    ..Here, we report a new E3 ligase for c-Myc, the carboxyl terminus of Hsc70-interacting protein or CHIP, which is a chaperone-associated Ubox-containing E3 ligase...
  4. Guo J, Ren F, Wang Y, Li S, Gao Z, Wang X, et al. miR-764-5p promotes osteoblast differentiation through inhibition of CHIP/STUB1 expression. J Bone Miner Res. 2012;27:1607-18 pubmed publisher
    ..We previously reported that C terminus of Hsc70-interacting protein/STIP1 homology and U-Box containing protein 1 (CHIP/STUB1) negatively regulated osteoblast differentiation through promoting Runx2 protein degradation...
  5. Min J, Whaley R, Sharpless N, Lockyer P, Portbury A, Patterson C. CHIP deficiency decreases longevity, with accelerated aging phenotypes accompanied by altered protein quality control. Mol Cell Biol. 2008;28:4018-25 pubmed publisher
    ..The carboxyl terminus of Hsp70-interacting protein (CHIP), a ubiquitin ligase/cochaperone, participates in protein quality control by targeting a broad range of chaperone ..
  6. Luo W, Zhong J, Chang R, Hu H, Pandey A, Semenza G. Hsp70 and CHIP selectively mediate ubiquitination and degradation of hypoxia-inducible factor (HIF)-1alpha but Not HIF-2alpha. J Biol Chem. 2010;285:3651-63 pubmed publisher
    ..Here, we identify Hsp70 and CHIP (carboxyl terminus of Hsc70-interacting protein) as HIF-1alpha-interacting proteins...
  7. Růcková E, Muller P, Nenutil R, Vojtesek B. Alterations of the Hsp70/Hsp90 chaperone and the HOP/CHIP co-chaperone system in cancer. Cell Mol Biol Lett. 2012;17:446-58 pubmed publisher
    ..cochaperones; therefore we investigated the expression of Hsp70 and Hsp90 and their specific co-chaperones HOP and CHIP in cancer cell lines and primary cancers...
  8. Arndt V, Daniel C, Nastainczyk W, Alberti S, Hohfeld J. BAG-2 acts as an inhibitor of the chaperone-associated ubiquitin ligase CHIP. Mol Biol Cell. 2005;16:5891-900 pubmed
    ..The cochaperone CHIP is of central importance on this pathway, because it acts as a chaperone-associated ubiquitin ligase...
  9. Graf C, Stankiewicz M, Nikolay R, Mayer M. Insights into the conformational dynamics of the E3 ubiquitin ligase CHIP in complex with chaperones and E2 enzymes. Biochemistry. 2010;49:2121-9 pubmed publisher
    The dimeric E3 ubiquitin ligase CHIP binds with its tetratricopeptide repeat (TPR) domain the C-terminus of molecular chaperones Hsp70 and Hsp90 and with its U-box region E2 ubiquitin-conjugating enzymes...
  10. Yan S, Sun X, Xiang B, Cang H, Kang X, Chen Y, et al. Redox regulation of the stability of the SUMO protease SENP3 via interactions with CHIP and Hsp90. EMBO J. 2010;29:3773-86 pubmed publisher
    ..heat shock protein 90 (Hsp90) and the co-chaperone/ubiquitin ligase carboxyl terminus of Hsc70-interacting protein (CHIP) control the turnover of client proteins...
  11. Narayan V, Pion E, Landré V, Muller P, Ball K. Docking-dependent ubiquitination of the interferon regulatory factor-1 tumor suppressor protein by the ubiquitin ligase CHIP. J Biol Chem. 2011;286:607-19 pubmed publisher
    ..Whereas CHIP (C terminus of Hsc70-interacting protein), appears to chaperone IRF-1 in unstressed cells, formation of a stable ..
  12. Matsumura Y, Sakai J, Skach W. Endoplasmic reticulum protein quality control is determined by cooperative interactions between Hsp/c70 protein and the CHIP E3 ligase. J Biol Chem. 2013;288:31069-79 pubmed publisher
    The C terminus of Hsp70 interacting protein (CHIP) E3 ligase functions as a key regulator of protein quality control by binding the C-terminal (M/I)EEVD peptide motif of Hsp/c70(90) with its N-terminal tetratricopeptide repeat (TPR) ..
  13. Shimura H, Schwartz D, Gygi S, Kosik K. CHIP-Hsc70 complex ubiquitinates phosphorylated tau and enhances cell survival. J Biol Chem. 2004;279:4869-76 pubmed
    ..Hsc70, and its phosphorylation is a recognition requirement for the addition of ubiquitin (Ub) by the E3 Ub ligase CHIP (carboxyl terminus of the Hsc70-interacting protein) and the E2 conjugating enzyme UbcH5B...
  14. Connell P, Ballinger C, Jiang J, Wu Y, Thompson L, Hohfeld J, et al. The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins. Nat Cell Biol. 2001;3:93-6 pubmed
    ..We previously identified CHIP (carboxyl terminus of Hsc70-interacting protein) to be an interaction partner of Hsc70 (ref. 4)...
  15. Parsons J, Tait P, Finch D, Dianova I, Allinson S, Dianov G. CHIP-mediated degradation and DNA damage-dependent stabilization regulate base excision repair proteins. Mol Cell. 2008;29:477-87 pubmed publisher
    ..on damaged DNA and that proteins not involved in a repair complex are ubiquitylated by the E3 ubiquitin ligase CHIP and subsequently rapidly degraded...
  16. Ko H, Bailey R, Smith W, Liu Z, Shin J, Lee Y, et al. CHIP regulates leucine-rich repeat kinase-2 ubiquitination, degradation, and toxicity. Proc Natl Acad Sci U S A. 2009;106:2897-902 pubmed publisher
    ..Here we show that the carboxyl terminus of HSP70-interacting protein (CHIP) binds, ubiquitinates, and promotes the ubiquitin proteasomal degradation of LRRK2...
  17. Alberti S, Böhse K, Arndt V, Schmitz A, Hohfeld J. The cochaperone HspBP1 inhibits the CHIP ubiquitin ligase and stimulates the maturation of the cystic fibrosis transmembrane conductance regulator. Mol Biol Cell. 2004;15:4003-10 pubmed
    The CHIP ubiquitin ligase turns molecular chaperones into protein degradation factors...
  18. Kumar P, Ambasta R, Veereshwarayya V, Rosen K, Kosik K, Band H, et al. CHIP and HSPs interact with beta-APP in a proteasome-dependent manner and influence Abeta metabolism. Hum Mol Genet. 2007;16:848-64 pubmed
    The C-terminus Hsp70 interacting protein (CHIP) has dual function as both co-chaperone and ubiquitin ligase...
  19. Hatakeyama S, Matsumoto M, Kamura T, Murayama M, Chui D, Planel E, et al. U-box protein carboxyl terminus of Hsc70-interacting protein (CHIP) mediates poly-ubiquitylation preferentially on four-repeat Tau and is involved in neurodegeneration of tauopathy. J Neurochem. 2004;91:299-307 pubmed
    ..Here, we show that carboxyl terminus of Hsc70-interacting protein (CHIP), a U-box protein, recognizes the microtubule-binding repeat region of tau and preferentially ubiquitylates four-..
  20. Nelson R, Glenn K, Miller V, Wen H, Paulson H. A novel route for F-box protein-mediated ubiquitination links CHIP to glycoprotein quality control. J Biol Chem. 2006;281:20242-51 pubmed
    ..ubiquitination of glycoproteins discarded from the endoplasmic reticulum, binds the co-chaperone/ubiquitin ligase CHIP (C terminus of Hsc-70-interacting protein) through a unique N-terminal PEST domain in Fbx2...
  21. Zhang L, Nephew K, Gallagher P. Regulation of death-associated protein kinase. Stabilization by HSP90 heterocomplexes. J Biol Chem. 2007;282:11795-804 pubmed
    ..Expression of two distinct ubiquitin E3 ligases, carboxyl terminus of HSC70-interacting protein (CHIP) or DIP1/Mib1, enhanced DAPK degradation, and conversely, short interfering RNA depletion of either CHIP or DIP1/..
  22. Kundrat L, Regan L. Identification of residues on Hsp70 and Hsp90 ubiquitinated by the cochaperone CHIP. J Mol Biol. 2010;395:587-94 pubmed publisher
    ..The ubiquitin ligase C-terminus of Hsc70 interacting protein (CHIP) has been shown in vitro and in vivo to associate with Hsp70 and Hsp90 and ubiquitinate them, thus targeting them ..
  23. Jan C, Yu C, Hung M, Harn H, Nieh S, Lee H, et al. Tid1, CHIP and ErbB2 interactions and their prognostic implications for breast cancer patients. J Pathol. 2011;225:424-37 pubmed publisher
    ..It is known that the carboxyl terminus of heat shock cognate 70 interacting protein (CHIP) efficiently down-regulates ErbB2 in vitro...
  24. Nie L, Wu H, Sun X. Ubiquitination and degradation of Tal1/SCL are induced by notch signaling and depend on Skp2 and CHIP. J Biol Chem. 2008;283:684-92 pubmed
    ..not only required Skp2, a substrate-binding subunit of SCF ubiquitin ligase complexes, but also relied on CHIP, a chaperone-binding protein with a ubiquitin ligase activity...
  25. Soss S, Yue Y, Dhe Paganon S, Chazin W. E2 conjugating enzyme selectivity and requirements for function of the E3 ubiquitin ligase CHIP. J Biol Chem. 2011;286:21277-86 pubmed publisher
    ..b>CHIP (carboxyl terminus of Hsc70-interacting protein) is a U-box E3 ligase that serves as a co-chaperone to heat shock ..
  26. Wen J, Luo K, Hu Y, Yang H, Fu J. Metastatic lymph node CHIP expression is a potential prognostic marker for resected esophageal squamous cell carcinoma patients. Ann Surg Oncol. 2013;20:1668-75 pubmed publisher
    C-terminal Hsp-interacting protein (CHIP) is an HSP70 and HSP90 interacting co-chaperone and an E3 ubiquitin ligase. Previous studies have reported the role of CHIP in cancer progression by targeting protein degradation...
  27. Tripathi V, Ali A, Bhat R, Pati U. CHIP chaperones wild type p53 tumor suppressor protein. J Biol Chem. 2007;282:28441-54 pubmed
    ..We have demonstrated that the co-chaperone CHIP (carboxyl terminus of Hsp70-interacting protein), which suppressed aggregation of several misfolded substrates and ..
  28. Kalia L, Kalia S, Chau H, Lozano A, Hyman B, McLean P. Ubiquitinylation of ?-synuclein by carboxyl terminus Hsp70-interacting protein (CHIP) is regulated by Bcl-2-associated athanogene 5 (BAG5). PLoS ONE. 2011;6:e14695 pubmed publisher
    ..We have previously shown that carboxyl terminus of Hsp70-interacting protein (CHIP), a co-chaperone molecule with E3 ubiquitin ligase activity, may reduce the levels of toxic ?-syn oligomers...
  29. Millan I, Squillace A, Gava L, Ramos C. The stability of wild-type and deletion mutants of human C-terminus Hsp70-interacting protein (CHIP). Protein Pept Lett. 2013;20:524-9 pubmed
    Carboxyl terminus of Hsp70 interacting protein (CHIP) is a dimeric co-chaperone involved in providing an appropriate balance between the synthesis and degradation of proteins, which is essential for normal cellular growth and function...
  30. Muller P, Růcková E, Halada P, Coates P, Hrstka R, Lane D, et al. C-terminal phosphorylation of Hsp70 and Hsp90 regulates alternate binding to co-chaperones CHIP and HOP to determine cellular protein folding/degradation balances. Oncogene. 2013;32:3101-10 pubmed publisher
    ..The mechanisms regulating these opposite activities involve Hsp binding to co-chaperones including CHIP and HOP at their C-termini...
  31. Imai Y, Soda M, Hatakeyama S, Akagi T, Hashikawa T, Nakayama K, et al. CHIP is associated with Parkin, a gene responsible for familial Parkinson's disease, and enhances its ubiquitin ligase activity. Mol Cell. 2002;10:55-67 pubmed
    ..Here, we show that CHIP, Hsp70, Parkin, and Pael-R formed a complex in vitro and in vivo...
  32. Xin H, Xu X, Li L, Ning H, Rong Y, Shang Y, et al. CHIP controls the sensitivity of transforming growth factor-beta signaling by modulating the basal level of Smad3 through ubiquitin-mediated degradation. J Biol Chem. 2005;280:20842-50 pubmed
    ..Here, we report evidence for a novel mechanism of regulating TGF-beta sensitivity that depends on the role of CHIP (carboxyl terminus of Hsc70-interacting protein) in regulating the basal level of Smad3 via the ubiquitin-dependent ..
  33. Rosser M, Washburn E, Muchowski P, Patterson C, Cyr D. Chaperone functions of the E3 ubiquitin ligase CHIP. J Biol Chem. 2007;282:22267-77 pubmed
    The carboxyl terminus of the Hsc70-interacting protein (CHIP) is an Hsp70 co-chaperone as well as an E3 ubiquitin ligase that protects cells from proteotoxic stress...
  34. Ding X, Goldberg M. Regulation of LRRK2 stability by the E3 ubiquitin ligase CHIP. PLoS ONE. 2009;4:e5949 pubmed publisher
    ..Here we show that the E3 ubiquitin ligase CHIP physically associates with LRRK2 and regulates the cellular abundance of LRRK2...
  35. Su C, Wang C, Lan K, Li C, Chao Y, Lin H, et al. Akt phosphorylation at Thr308 and Ser473 is required for CHIP-mediated ubiquitination of the kinase. Cell Signal. 2011;23:1824-30 pubmed publisher
    ..We show here that Thr308 and Ser473 phosphorylations prompt Akt to enter the CHIP-mediated ubiquitin-proteasome pathway...
  36. Jang K, Lee K, Kim S, Jin T, Choi E, Jeon H, et al. Ubiquitin ligase CHIP induces TRAF2 proteasomal degradation and NF-?B inactivation to regulate breast cancer cell invasion. J Cell Biochem. 2011;112:3612-20 pubmed publisher
    ..The carboxyl terminus of Hsc70-interacting protein (CHIP) is a U-box-type ubiquitin ligase that induces ubiquitination and proteasomal degradation of its substrate proteins...
  37. Ballinger C, Connell P, Wu Y, Hu Z, Thompson L, Yin L, et al. Identification of CHIP, a novel tetratricopeptide repeat-containing protein that interacts with heat shock proteins and negatively regulates chaperone functions. Mol Cell Biol. 1999;19:4535-45 pubmed
    ..proteins, we have identified a novel 35-kDa cytoplasmic protein, carboxyl terminus of Hsc70-interacting protein (CHIP). CHIP is highly expressed in adult striated muscle in vivo and is expressed broadly in vitro in tissue culture...
  38. Dickey C, Kamal A, Lundgren K, Klosak N, Bailey R, Dunmore J, et al. The high-affinity HSP90-CHIP complex recognizes and selectively degrades phosphorylated tau client proteins. J Clin Invest. 2007;117:648-58 pubmed
    ..A critical mediator of this mechanism was carboxy terminus of Hsp70-interacting protein (CHIP), a tau ubiquitin ligase...
  39. Li D, Marchenko N, Schulz R, Fischer V, Velasco Hernandez T, Talos F, et al. Functional inactivation of endogenous MDM2 and CHIP by HSP90 causes aberrant stabilization of mutant p53 in human cancer cells. Mol Cancer Res. 2011;9:577-88 pubmed publisher
    ..p53 cancer cells, we show that in mutant p53 cancer cells, this HSP90 interaction blocks the endogenous MDM2 and CHIP (carboxy-terminus of Hsp70-interacting protein) E3 ligase activity...
  40. Sahara N, Murayama M, Mizoroki T, Urushitani M, Imai Y, Takahashi R, et al. In vivo evidence of CHIP up-regulation attenuating tau aggregation. J Neurochem. 2005;94:1254-63 pubmed
    The carboxyl terminus of heat-shock cognate (Hsc)70-interacting protein (CHIP) is a ubiquitin E3 ligase that can collaborate with molecular chaperones to facilitate protein folding and prevent protein aggregation...
  41. Windheim M, Peggie M, Cohen P. Two different classes of E2 ubiquitin-conjugating enzymes are required for the mono-ubiquitination of proteins and elongation by polyubiquitin chains with a specific topology. Biochem J. 2008;409:723-9 pubmed
    ..For this reason, chain topology must be tightly controlled. Using the U-box E3 ligase CHIP [C-terminus of the Hsc (heat-shock cognate) 70-interacting protein] and the RING E3 ligase TRAF6 (tumour-necrosis-..
  42. Woo C, Le N, Shishido T, Chang E, Lee H, Heo K, et al. Novel role of C terminus of Hsc70-interacting protein (CHIP) ubiquitin ligase on inhibiting cardiac apoptosis and dysfunction via regulating ERK5-mediated degradation of inducible cAMP early repressor. FASEB J. 2010;24:4917-28 pubmed publisher
    ..A cardioprotective effect of ubiquitin (Ub) ligase of the C terminus of Hsc70-interacting protein (CHIP) on myocytes has been reported...
  43. Xu T, Zhou Q, Zhou J, Huang Y, Yan Y, Li W, et al. Carboxyl terminus of Hsp70-interacting protein (CHIP) contributes to human glioma oncogenesis. Cancer Sci. 2011;102:959-66 pubmed publisher
    ..Growing evidence has shown that E3 ubiquitin ligases can promote tumorgenesis of glioma. CHIP is an E3 ubiquitin ligase that can induce ubiquitylation and degradation of many tumor-related proteins, and it has ..
  44. Ferreira J, Fôfo H, Bejarano E, Bento C, Ramalho J, Girao H, et al. STUB1/CHIP is required for HIF1A degradation by chaperone-mediated autophagy. Autophagy. 2013;9:1349-66 pubmed publisher
  45. Zhang M, Windheim M, Roe S, Peggie M, Cohen P, Prodromou C, et al. Chaperoned ubiquitylation--crystal structures of the CHIP U box E3 ubiquitin ligase and a CHIP-Ubc13-Uev1a complex. Mol Cell. 2005;20:525-38 pubmed
    b>CHIP is a dimeric U box E3 ubiquitin ligase that binds Hsp90 and/or Hsp70 via its TPR-domain, facilitating ubiquitylation of chaperone bound client proteins...
  46. Wang T, Yang J, Xu J, Li J, Cao Z, Zhou L, et al. CHIP is a novel tumor suppressor in pancreatic cancer through targeting EGFR. Oncotarget. 2014;5:1969-86 pubmed
    Carboxyl terminus of heat shock protein 70-interacting protein (CHIP) is an E3 ubiquitin ligase that is involved in protein quality control and mediates several tumor-related proteins in many cancers, but the function of CHIP in ..
  47. Huen M, Huang J, Yuan J, Yamamoto M, Akira S, Ashley C, et al. Noncanonical E2 variant-independent function of UBC13 in promoting checkpoint protein assembly. Mol Cell Biol. 2008;28:6104-12 pubmed publisher
    ..We propose that the RNF8 RING domain selects and loads a subset of UBC13 molecules, distinct from those that exist as heterodimers, onto sites of double-strand breaks, which facilitates the amplification of DNA damage signals. ..
  48. Choi Y, Lee S, Seo T, Lee J, Yoo S. C-Terminus of Hsc70-interacting protein regulates profilin1 and breast cancer cell migration. Biochem Biophys Res Commun. 2014;446:1060-6 pubmed publisher
    ..C-terminus of Hsc70-interacting protein (CHIP), a co-chaperone E3 ligase, interacts with and ubiquitinates Pfn1, targeting it for proteasome-dependent ..
  49. Jiang J, Ballinger C, Wu Y, Dai Q, Cyr D, Hohfeld J, et al. CHIP is a U-box-dependent E3 ubiquitin ligase: identification of Hsc70 as a target for ubiquitylation. J Biol Chem. 2001;276:42938-44 pubmed
    ..b>CHIP (carboxyl terminus of Hsc70-interacting protein) is such a cofactor that interacts with Hsc70 and, in general, ..
  50. Urushitani M, Kurisu J, Tateno M, Hatakeyama S, Nakayama K, Kato S, et al. CHIP promotes proteasomal degradation of familial ALS-linked mutant SOD1 by ubiquitinating Hsp/Hsc70. J Neurochem. 2004;90:231-44 pubmed
    ..heat-shock protein (Hsp) or heat-shock cognate (Hsc)70, and the carboxyl terminus of the Hsc70-interacting protein (CHIP), are involved in proteasomal degradation of mutant SOD1...
  51. Huang Z, Nie L, Xu M, Sun X. Notch-induced E2A degradation requires CHIP and Hsc70 as novel facilitators of ubiquitination. Mol Cell Biol. 2004;24:8951-62 pubmed
    ..we conducted a yeast two-hybrid screen and identified the carboxyl terminus of Hsc70-interacting protein (CHIP) as an E47 binding protein...
  52. Shimamoto S, Kubota Y, Yamaguchi F, Tokumitsu H, Kobayashi R. Ca2+/S100 proteins act as upstream regulators of the chaperone-associated ubiquitin ligase CHIP (C terminus of Hsc70-interacting protein). J Biol Chem. 2013;288:7158-68 pubmed publisher
    The U-box E3 ubiquitin ligase CHIP (C terminus of Hsc70-interacting protein) binds Hsp90 and/or Hsp70 via its tetratricopeptide repeat (TPR), facilitating ubiquitination of the chaperone-bound client proteins...
  53. Chen Z, Barbi J, Bu S, Yang H, Li Z, Gao Y, et al. The ubiquitin ligase Stub1 negatively modulates regulatory T cell suppressive activity by promoting degradation of the transcription factor Foxp3. Immunity. 2013;39:272-85 pubmed publisher
  54. Qian S, McDonough H, Boellmann F, Cyr D, Patterson C. CHIP-mediated stress recovery by sequential ubiquitination of substrates and Hsp70. Nature. 2006;440:551-5 pubmed
    ..b>CHIP (carboxy terminus of Hsp70-binding protein), a dual-function co-chaperone/ubiquitin ligase, targets a broad range ..
  55. Shi Y, Wang J, Li J, Ren H, Guan W, He M, et al. Identification of CHIP as a novel causative gene for autosomal recessive cerebellar ataxia. PLoS ONE. 2013;8:e81884 pubmed publisher
    ..493CT) in CHIP (NM_005861) in this family. Using Sanger sequencing, we also identified two compound heterozygous mutations (c...
  56. Depondt C, Donatello S, Simonis N, Rai M, Van Heurck R, Abramowicz M, et al. Autosomal recessive cerebellar ataxia of adult onset due to STUB1 mutations. Neurology. 2014;82:1749-50 pubmed publisher
    ..Friedreich ataxia accounts for one-third of the cases in Caucasians; the others are due to a growing list of very rare molecular defects, including mild forms of metabolic diseases. In nearly 50%, the genetic cause remains undetermined. ..
  57. Hampe C, Ardila Osorio H, Fournier M, Brice A, Corti O. Biochemical analysis of Parkinson's disease-causing variants of Parkin, an E3 ubiquitin-protein ligase with monoubiquitylation capacity. Hum Mol Genet. 2006;15:2059-75 pubmed
    ..vitro assay, Parkin catalyzed the linkage of single ubiquitin molecules only, whereas the ubiquitin-protein ligases CHIP and Mdm2 promoted the formation of polyubiquitin chains...
  58. Tsvetkov P, Adamovich Y, Elliott E, Shaul Y. E3 ligase STUB1/CHIP regulates NAD(P)H:quinone oxidoreductase 1 (NQO1) accumulation in aged brain, a process impaired in certain Alzheimer disease patients. J Biol Chem. 2011;286:8839-45 pubmed publisher
    ..We show here that NQO1 protein level is regulated by the E3 ligase STUB1/CHIP (C terminus of Hsc70-interacting protein)...
  59. Petrucelli L, Dickson D, Kehoe K, Taylor J, Snyder H, Grover A, et al. CHIP and Hsp70 regulate tau ubiquitination, degradation and aggregation. Hum Mol Genet. 2004;13:703-14 pubmed
    ..g. tau and alpha-synuclein respectively). Here we report that CHIP, an ubiquitin ligase that interacts directly with Hsp70/90, induces ubiquitination of the microtubule associated ..
  60. He B, Bai S, Hnat A, Kalman R, Minges J, Patterson C, et al. An androgen receptor NH2-terminal conserved motif interacts with the COOH terminus of the Hsp70-interacting protein (CHIP). J Biol Chem. 2004;279:30643-53 pubmed
    ..was suggested from a yeast two-hybrid screen that identified the COOH terminus of the Hsp70-interacting protein (CHIP) as a binding partner...
  61. Shin Y, Klucken J, Patterson C, Hyman B, McLean P. The co-chaperone carboxyl terminus of Hsp70-interacting protein (CHIP) mediates alpha-synuclein degradation decisions between proteasomal and lysosomal pathways. J Biol Chem. 2005;280:23727-34 pubmed
    ..In the current study, we investigate the role of the carboxyl terminus of Hsp70-interacting protein (CHIP) in alpha-synuclein aggregation...
  62. Xia T, Dimitropoulou C, Zeng J, Antonova G, Snead C, Venema R, et al. Chaperone-dependent E3 ligase CHIP ubiquitinates and mediates proteasomal degradation of soluble guanylyl cyclase. Am J Physiol Heart Circ Physiol. 2007;293:H3080-7 pubmed
    ..In this study, we have investigated whether COOH terminus of heat shock protein 70-interacting protein (CHIP), a co-chaperone molecule that is involved in protein folding but is also a chaperone-dependent ubiquitin E3 ligase,..
  63. Shang Y, Zhao X, Xu X, Xin H, Li X, Zhai Y, et al. CHIP functions an E3 ubiquitin ligase of Runx1. Biochem Biophys Res Commun. 2009;386:242-6 pubmed publisher
    ..Improper expression and mutations in Runx1 are frequently implicated in human leukemia. Here, we report that CHIP, the carboxyl terminus of Hsc70-interacting protein, also named Stub1, physically interacts with Runx1 through the ..
  64. Li L, Xin H, Xu X, Huang M, Zhang X, Chen Y, et al. CHIP mediates degradation of Smad proteins and potentially regulates Smad-induced transcription. Mol Cell Biol. 2004;24:856-64 pubmed
    ..the regulation of SMAD-mediated signaling, by which the Smad1 protein level is controlled through expression of the CHIP protein. CHIP is a U-box-dependent E3 ubiquitin ligase, previously identified as a cochaperon protein...
  65. Lee J, Khadka P, Baek S, Chung I. CHIP promotes human telomerase reverse transcriptase degradation and negatively regulates telomerase activity. J Biol Chem. 2010;285:42033-45 pubmed publisher
    ..Here, we show that CHIP (C terminus of Hsc70-interacting protein) physically associates with hTERT in the cytoplasm and regulates the ..
  66. Shi C, Schisler J, Rubel C, Tan S, Song B, McDonough H, et al. Ataxia and hypogonadism caused by the loss of ubiquitin ligase activity of the U box protein CHIP. Hum Mol Genet. 2014;23:1013-24 pubmed publisher
    ..737C?T, p.Thr246Met, a gene that encodes the protein CHIP (C-terminus of HSC70-interacting protein)...
  67. Zhou P, Fernandes N, Dodge I, Reddi A, Rao N, Safran H, et al. ErbB2 degradation mediated by the co-chaperone protein CHIP. J Biol Chem. 2003;278:13829-37 pubmed
    ..Here, we show that ErbB2 serves as an in vitro substrate for the Hsp70/Hsp90-associated U-box ubiquitin ligase CHIP. Overexpression of wild type CHIP, but not its U-box mutant H260Q, induced ubiquitinylation and reduction in both ..
  68. Oh K, Yang S, Park J, Seol J, Iemura S, Natsume T, et al. Control of AIF-mediated cell death by antagonistic functions of CHIP ubiquitin E3 ligase and USP2 deubiquitinating enzyme. Cell Death Differ. 2011;18:1326-36 pubmed publisher
    ..Here, we demonstrated that USP2 and CHIP contribute to the control of tAIF stability...
  69. Plechanovová A, Jaffray E, Tatham M, Naismith J, Hay R. Structure of a RING E3 ligase and ubiquitin-loaded E2 primed for catalysis. Nature. 2012;489:115-20 pubmed publisher
    ..This arrangement is primed for catalysis as it can deprotonate the incoming substrate lysine residue and stabilize the consequent tetrahedral transition-state intermediate. ..
  70. Tsuchiya M, Nakajima Y, Hirata N, Morishita T, Kishimoto H, Kanda Y, et al. Ubiquitin ligase CHIP suppresses cancer stem cell properties in a population of breast cancer cells. Biochem Biophys Res Commun. 2014;452:928-32 pubmed publisher
    ..In our previous study, we showed that a ubiquitin E3 ligase carboxyl terminus of Hsc70-interacting protein (CHIP) suppressed breast cancer malignancy...
  71. Meacham G, Patterson C, Zhang W, Younger J, Cyr D. The Hsc70 co-chaperone CHIP targets immature CFTR for proteasomal degradation. Nat Cell Biol. 2001;3:100-5 pubmed
    ..b>CHIP is a cytosolic U-box protein that interacts with Hsc70 through a set of tetratricorepeat motifs...
  72. Murata S, Minami Y, Minami M, Chiba T, Tanaka K. CHIP is a chaperone-dependent E3 ligase that ubiquitylates unfolded protein. EMBO Rep. 2001;2:1133-8 pubmed
    ..Here, we report that the C-terminus of Hsc70-interacting protein (CHIP) with a U-box domain is an E3 ubiquitin-ligase collaborating with molecular chaperones Hsp90 and Hsc70...
  73. Westhoff B, Chapple J, van der Spuy J, Hohfeld J, Cheetham M. HSJ1 is a neuronal shuttling factor for the sorting of chaperone clients to the proteasome. Curr Biol. 2005;15:1058-64 pubmed
    ..In this way, HSJ1 isoforms participate in ER-associated degradation (ERAD) and protect neurons against cytotoxic protein aggregation. ..
  74. Ishigaki S, Niwa J, Yamada S, Takahashi M, Ito T, Sone J, et al. Dorfin-CHIP chimeric proteins potently ubiquitylate and degrade familial ALS-related mutant SOD1 proteins and reduce their cellular toxicity. Neurobiol Dis. 2007;25:331-41 pubmed
    ..hydrophobic portion of Dorfin and the U-box domain of the carboxyl terminus of Hsc70-interacting protein (CHIP), which has strong E3 activity through the U-box domain...
  75. Kim H, Kim K, Lledias F, Kisselev A, Scaglione K, Skowyra D, et al. Certain pairs of ubiquitin-conjugating enzymes (E2s) and ubiquitin-protein ligases (E3s) synthesize nondegradable forked ubiquitin chains containing all possible isopeptide linkages. J Biol Chem. 2007;282:17375-86 pubmed
    ..purified E3s and Ub-conjugating enzymes (E2s), we found, using Ub mutants and mass spectrometry, that the U-box E3, CHIP, and Ring finger E3s, MuRF1 and Mdm2, with the E2, UbcH5, form a novel type of Ub chain that contains all seven ..
  76. Tateishi Y, Kawabe Y, Chiba T, Murata S, Ichikawa K, Murayama A, et al. Ligand-dependent switching of ubiquitin-proteasome pathways for estrogen receptor. EMBO J. 2004;23:4813-23 pubmed
    ..unliganded ERalpha and identified a protein complex containing the carboxyl terminus of Hsc70-interacting protein (CHIP). CHIP preferentially bound to misfolded ERalpha and ubiquitinated it to induce degradation...
  77. Dai Q, Qian S, Li H, McDonough H, Borchers C, Huang D, et al. Regulation of the cytoplasmic quality control protein degradation pathway by BAG2. J Biol Chem. 2005;280:38673-81 pubmed
    ..b>CHIP (carboxyl terminus of Hsp70-interacting protein) is an Hsp70-associated ubiquitin ligase that participates in this ..
  78. Al Ramahi I, Lam Y, Chen H, de Gouyon B, Zhang M, Perez A, et al. CHIP protects from the neurotoxicity of expanded and wild-type ataxin-1 and promotes their ubiquitination and degradation. J Biol Chem. 2006;281:26714-24 pubmed
    b>CHIP (C terminus of Hsc-70 interacting protein) is an E3 ligase that links the protein folding machinery with the ubiquitin-proteasome system and has been implicated in disorders characterized by protein misfolding and aggregation...
  79. Jung Y, Xu W, Kim H, Ha N, Neckers L. Curcumin-induced degradation of ErbB2: A role for the E3 ubiquitin ligase CHIP and the Michael reaction acceptor activity of curcumin. Biochim Biophys Acta. 2007;1773:383-90 pubmed
    ..Curcumin increased association of endogenous and ectopically expressed CHIP, a chaperone-dependent ubiquitin ligase, with ErbB2...
  80. Jang K, Lee J, Kim S, Kang M, Na M, Lee C, et al. The C-terminus of Hsp70-interacting protein promotes Met receptor degradation. J Thorac Oncol. 2011;6:679-87 pubmed publisher
    ..Met receptor interacted with the C-terminus of heat shock protein 70-interacting protein (CHIP), leading to proteasomal degradation of the receptor in vitro...
  81. Ahmed S, Deb S, Paul I, Chatterjee A, Mandal T, Chatterjee U, et al. The chaperone-assisted E3 ligase C terminus of Hsc70-interacting protein (CHIP) targets PTEN for proteasomal degradation. J Biol Chem. 2012;287:15996-6006 pubmed publisher
    ..Nedd 4-1, XIAP, and WWP2 have been shown to maintain PTEN turnover. Here, we report that CHIP, the chaperone-associated E3 ligase, induces ubiquitination and regulates the proteasomal turnover of PTEN...
  82. Donnelly B, Needham P, Snyder A, Roy A, Khadem S, Brodsky J, et al. Hsp70 and Hsp90 multichaperone complexes sequentially regulate thiazide-sensitive cotransporter endoplasmic reticulum-associated degradation and biogenesis. J Biol Chem. 2013;288:13124-35 pubmed publisher
    ..In addition, two cochaperones, the C terminus of Hsp70-interacting protein (CHIP) and the Hsp70/Hsp90 organizer protein, were associated with NCC...
  83. Kajiro M, Hirota R, Nakajima Y, Kawanowa K, So ma K, Ito I, et al. The ubiquitin ligase CHIP acts as an upstream regulator of oncogenic pathways. Nat Cell Biol. 2009;11:312-9 pubmed publisher
    b>CHIP is a U-box-type ubiquitin ligase that induces ubiquitylation and degradation of its substrates, which include several oncogenic proteins. The relationship between CHIP and tumour progression, however, has not been elucidated...
  84. Li R, Shang Y, Liu D, Ren Z, Chang Z, Sui S. Differential ubiquitination of Smad1 mediated by CHIP: implications in the regulation of the bone morphogenetic protein signaling pathway. J Mol Biol. 2007;374:777-90 pubmed
    ..and K269) of Smad1 are ubiquitin acceptor sites mediated by the carboxyl terminus of Hsc70-interacting protein (CHIP)...
  85. Rao S, Sharma J, Maity R, Jana N. Co-chaperone CHIP stabilizes aggregate-prone malin, a ubiquitin ligase mutated in Lafora disease. J Biol Chem. 2010;285:1404-13 pubmed publisher
    ..Finally, we demonstrate that the co-chaperone carboxyl terminus of the Hsc70-interacting protein (CHIP) stabilizes malin by modulating the activity of Hsp70...
  86. Maruyama T, Kadowaki H, Okamoto N, Nagai A, Naguro I, Matsuzawa A, et al. CHIP-dependent termination of MEKK2 regulates temporal ERK activation required for proper hyperosmotic response. EMBO J. 2010;29:2501-14 pubmed publisher
    ..Moreover, we identified the E3 ubiquitin ligase carboxyl terminus of Hsc70-interacting protein (CHIP) as a binding partner of MEKK2...
  87. Wang S, Wu X, Zhang J, Chen Y, Xu J, Xia X, et al. CHIP functions as a novel suppressor of tumour angiogenesis with prognostic significance in human gastric cancer. Gut. 2013;62:496-508 pubmed publisher
    b>CHIP (carboxy terminus of Hsc70 interacting protein) is an E3 ubiquitin ligase that can induce ubiquitination and degradation of several tumour related proteins, and acts as a suppressor of tumour metastasis...
  88. Wang Y, Ren F, Wang Y, Feng Y, Wang D, Jia B, et al. CHIP/Stub1 functions as a tumor suppressor and represses NF-?B-mediated signaling in colorectal cancer. Carcinogenesis. 2014;35:983-91 pubmed publisher
    The carboxyl terminus of Hsc70-interacting protein (CHIP, also named Stub1), a U-box containing E3 ubiquitin ligase, is involved in degradation of certain oncogenic proteins...
  89. Demand J, Alberti S, Patterson C, Hohfeld J. Cooperation of a ubiquitin domain protein and an E3 ubiquitin ligase during chaperone/proteasome coupling. Curr Biol. 2001;11:1569-77 pubmed
    ..By characterizing the chaperone cofactors BAG-1 and CHIP, we gained insight into the cooperation of the molecular chaperones Hsc70 and Hsp70 with the ubiquitin/proteasome ..
  90. Xu W, Marcu M, Yuan X, Mimnaugh E, Patterson C, Neckers L. Chaperone-dependent E3 ubiquitin ligase CHIP mediates a degradative pathway for c-ErbB2/Neu. Proc Natl Acad Sci U S A. 2002;99:12847-52 pubmed
    ..We now show that the chaperone-binding ubiquitin ligase CHIP efficiently ubiquitinates and down-regulates ErbB2...
  91. Nikolay R, Wiederkehr T, Rist W, Kramer G, Mayer M, Bukau B. Dimerization of the human E3 ligase CHIP via a coiled-coil domain is essential for its activity. J Biol Chem. 2004;279:2673-8 pubmed
    The Hsp70-interacting E3-ubiquitin ligase CHIP has been implicated in the decision as to whether a target protein enters the refolding or the degradation pathway...