Gene Symbol: Stub1
Description: STIP1 homology and U-Box containing protein 1
Alias: 0610033N24Rik, 2210017D18Rik, 2310040B03Rik, AW046544, Chip, STIP1 homology and U box-containing protein 1, E3 ubiquitin-protein ligase CHIP, RING-type E3 ubiquitin transferase CHIP, carboxy terminus of Hsp70-interacting protein
Species: mouse
Products:     Stub1

Top Publications

  1. 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...
  2. Jana N, Dikshit P, Goswami A, Kotliarova S, Murata S, Tanaka K, et al. Co-chaperone CHIP associates with expanded polyglutamine protein and promotes their degradation by proteasomes. J Biol Chem. 2005;280:11635-40 pubmed
    ..Here, we demonstrate that CHIP (C terminus of Hsp70-interacting protein) co-immunoprecipitates with the polyglutamine-expanded huntingtin or ..
  3. 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...
  4. 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...
  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. 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...
  7. Adachi H, Waza M, Tokui K, Katsuno M, Minamiyama M, Tanaka F, et al. CHIP overexpression reduces mutant androgen receptor protein and ameliorates phenotypes of the spinal and bulbar muscular atrophy transgenic mouse model. J Neurosci. 2007;27:5115-26 pubmed
    ..C terminus of Hsc70 (heat shock cognate protein 70)-interacting protein (CHIP), a U-box type E3 ubiquitin ligase, has been shown to interact with heat shock protein 90 (Hsp90) or Hsp70 and ..
  8. 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 ..
  9. 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 ..

More Information


  1. 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...
  2. 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...
  3. McDonough H, Charles P, Hilliard E, Qian S, Min J, Portbury A, et al. Stress-dependent Daxx-CHIP interaction suppresses the p53 apoptotic program. J Biol Chem. 2009;284:20649-59 pubmed publisher
    Our previous studies have implicated CHIP (carboxyl terminus of Hsp70-interacting protein) as a co-chaperone/ubiquitin ligase whose activities yield protection against stress-induced apoptotic events...
  4. 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...
  5. 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...
  6. Dickey C, Yue M, Lin W, Dickson D, Dunmore J, Lee W, et al. Deletion of the ubiquitin ligase CHIP leads to the accumulation, but not the aggregation, of both endogenous phospho- and caspase-3-cleaved tau species. J Neurosci. 2006;26:6985-96 pubmed
    ..We hypothesized that depletion of CHIP, a tau ubiquitin ligase, would lead to an increase in abnormal tau...
  7. 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 ..
  8. 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 ..
  9. 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...
  10. 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...
  11. 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...
  12. Stankowski J, Zeiger S, Cohen E, DeFranco D, Cai J, McLaughlin B. C-terminus of heat shock cognate 70 interacting protein increases following stroke and impairs survival against acute oxidative stress. Antioxid Redox Signal. 2011;14:1787-801 pubmed publisher
    ..Overexpression of the ubiquitin ligase C-terminus of HSC70 interacting protein (CHIP) can compensate for failure of other ubiquitin ligases and enhance protein turnover and survival under chronic ..
  13. Hatakeyama S, Yada M, Matsumoto M, Ishida N, Nakayama K. U box proteins as a new family of ubiquitin-protein ligases. J Biol Chem. 2001;276:33111-20 pubmed
    ..These data suggest that U box proteins constitute a third family of E3 enzymes and that E4 activity may reflect a specialized type of E3 activity. ..
  14. Fukunishi Y, Suzuki H, Yoshino M, Konno H, Hayashizaki Y. Prediction of human cDNA from its homologous mouse full-length cDNA and human shotgun database. FEBS Lett. 1999;464:129-32 pubmed
    ..The accuracy of the predicted human full-length coding region is 83.3%, and the false positive rate is 16.7%. Five human full-length proteins out of 20 proteins are correctly predicted. ..
  15. Yang M, Wang C, Zhu X, Tang S, Shi L, Cao X, et al. E3 ubiquitin ligase CHIP facilitates Toll-like receptor signaling by recruiting and polyubiquitinating Src and atypical PKC{zeta}. J Exp Med. 2011;208:2099-112 pubmed publisher
    The carboxyl terminus of constitutive heat shock cognate 70 (HSC70)-interacting protein (CHIP, also known as Stub1) is a U box-containing E3 ubiquitin ligase that is important for protein quality control...
  16. 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
    ..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...
  17. Teng Y, Rezvani K, De Biasi M. UBXN2A regulates nicotinic receptor degradation by modulating the E3 ligase activity of CHIP. Biochem Pharmacol. 2015;97:518-530 pubmed publisher
    ..Further investigation of the mechanisms of UBXN2A actions revealed that the protein interacts with CHIP (carboxyl terminus of Hsc70 interacting protein), whose ubiquitin E3 ligase activity regulates the degradation of ..
  18. Wei Q, Sha Y, Bhattacharya A, Abdel Fattah E, Bonilla D, Jyothula S, et al. Regulation of IL-4 receptor signaling by STUB1 in lung inflammation. Am J Respir Crit Care Med. 2014;189:16-29 pubmed publisher
    ..To evaluate the role of STUB1 (STIP1 homology and U-Box containing protein 1) in regulating IL-4R signaling in airway inflammation...
  19. Zhang C, Xu Z, He X, Michael L, Patterson C. CHIP, a cochaperone/ubiquitin ligase that regulates protein quality control, is required for maximal cardioprotection after myocardial infarction in mice. Am J Physiol Heart Circ Physiol. 2005;288:H2836-42 pubmed
    ..b>CHIP (carboxyl terminus of Hsp70-interacting protein) is a cochaperone/ubiquitin ligase that integrates the response to ..
  20. Del Prete D, Rice R, Rajadhyaksha A, D ADAMIO L. Amyloid Precursor Protein (APP) May Act as a Substrate and a Recognition Unit for CRL4CRBN and Stub1 E3 Ligases Facilitating Ubiquitination of Proteins Involved in Presynaptic Functions and Neurodegeneration. J Biol Chem. 2016;291:17209-27 pubmed publisher
    ..with proteins that regulate the ubiquitin-proteasome system, predominantly with the E3 ubiquitin-protein ligases Stub1, which binds the NH2 terminus of the ACR, and CRL4(CRBN), which is formed by Cul4a/b, Ddb1, and Crbn, and ..
  21. Li S, Shu B, Zhang Y, Li J, Guo J, Wang Y, et al. Carboxyl terminus of Hsp70-interacting protein regulation of osteoclast formation in mice through promotion of tumor necrosis factor receptor-associated factor 6 protein degradation. Arthritis Rheumatol. 2014;66:1854-63 pubmed publisher
    Carboxyl terminus of Hsp70-interacting protein (CHIP or STUB1) is an E3 ligase that regulates the stability of several proteins involved in tumor growth and metastasis...
  22. Hatakeyama S, Matsumoto M, Yada M, Nakayama K. Interaction of U-box-type ubiquitin-protein ligases (E3s) with molecular chaperones. Genes Cells. 2004;9:533-48 pubmed
    ..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 ..
  23. Ko H, Kim C, Lee S, Song J, Lee K, Kim K, et al. P42 Ebp1 regulates the proteasomal degradation of the p85 regulatory subunit of PI3K by recruiting a chaperone-E3 ligase complex HSP70/CHIP. Cell Death Dis. 2014;5:e1131 pubmed publisher
    ..Importantly, we found that p42 induces protein degradation of the p85 subunit and further identified HSP70/CHIP complex as a novel E3 ligase for p85 that is responsible for p85 ubiquitination and degradation...
  24. Lim S, Miller N, Chen X, Tancioni I, Walsh C, Lawson C, et al. Nuclear-localized focal adhesion kinase regulates inflammatory VCAM-1 expression. J Cell Biol. 2012;197:907-19 pubmed publisher
    ..1, ezrin, radixin, moesin homology) domain bound directly to GATA4 and enhanced its CHIP (C terminus of Hsp70-interacting protein) E3 ligase-dependent polyubiquitination and degradation...
  25. Jiang J, Cyr D, Babbitt R, Sessa W, Patterson C. Chaperone-dependent regulation of endothelial nitric-oxide synthase intracellular trafficking by the co-chaperone/ubiquitin ligase CHIP. J Biol Chem. 2003;278:49332-41 pubmed
    ..Hsp90 is modulated by physical interaction with its co-chaperones. CHIP (carboxyl terminus of Hsp70-interacting protein) is such a co-chaperone that remodels the Hsp90 heterocomplex and ..
  26. Li X, Huang M, Zheng H, Wang Y, Ren F, Shang Y, et al. CHIP promotes Runx2 degradation and negatively regulates osteoblast differentiation. J Cell Biol. 2008;181:959-72 pubmed publisher
    ..In this paper, we report that CHIP (C terminus of Hsc70-interacting protein)/STUB1 regulates Runx2 protein stability via a ubiquitination-degradation mechanism...
  27. Wang X, DeFranco D. Alternative effects of the ubiquitin-proteasome pathway on glucocorticoid receptor down-regulation and transactivation are mediated by CHIP, an E3 ligase. Mol Endocrinol. 2005;19:1474-82 pubmed, we show that stable overexpression of the carboxy terminus of heat shock protein 70-interacting protein (CHIP) E3 ligase can restore hormone-dependent down-regulation of GR in HT22 cells...
  28. Seo J, Lee E, Song J. New role of E3 ubiquitin ligase in the regulation of necroptosis. BMB Rep. 2016;49:247-8 pubmed
    ..Our recent studies have revealed that C-terminus HSC-70 interacting protein (CHIP), an E3 ligase, can function as an inhibitor of necroptosis...
  29. McLaughlin B, Buendia M, Saborido T, Palubinsky A, Stankowski J, Stanwood G. Haploinsufficiency of the E3 ubiquitin ligase C-terminus of heat shock cognate 70 interacting protein (CHIP) produces specific behavioral impairments. PLoS ONE. 2012;7:e36340 pubmed publisher
    The multifunctional E3 ubiquitin ligase CHIP is an essential interacting partner of HSP70, which together promote the proteasomal degradation of client proteins...
  30. Scaglione K, Zavodszky E, Todi S, Patury S, Xu P, Rodriguez Lebron E, et al. Ube2w and ataxin-3 coordinately regulate the ubiquitin ligase CHIP. Mol Cell. 2011;43:599-612 pubmed publisher
    ..Here we describe a series of molecular events that coordinately regulate CHIP, a neuroprotective E3 implicated in protein quality control...
  31. Radovanac K, Morgner J, Schulz J, Blumbach K, Patterson C, Geiger T, et al. Stabilization of integrin-linked kinase by the Hsp90-CHIP axis impacts cellular force generation, migration and the fibrotic response. EMBO J. 2013;32:1409-24 pubmed publisher
    ..The mechanisms by which ILK stability and turnover are regulated are unknown. Here we report that the E3 ligase CHIP-heat shock protein 90 (Hsp90) axis regulates ILK turnover in fibroblasts...
  32. Xu C, Zhang T, Wang H, Yang H, Li H. CHIP enhances angiogenesis and restores cardiac function after infarction in transgenic mice. Cell Physiol Biochem. 2013;31:199-208 pubmed publisher
    Carboxyl terminus of Hsp70-interacting protein (CHIP) is a chaperone/ubiquitin ligase that plays an important role in stress-induced apoptosis...
  33. Wang H, Yu X, Guo C, Zuo D, Fisher P, Subjeck J, et al. Enhanced endoplasmic reticulum entry of tumor antigen is crucial for cross-presentation induced by dendritic cell-targeted vaccination. J Immunol. 2013;191:6010-21 pubmed publisher
    ..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. ..
  34. Faresse N, Ruffieux Daidié D, Salamin M, Gomez Sanchez C, Staub O. Mineralocorticoid receptor degradation is promoted by Hsp90 inhibition and the ubiquitin-protein ligase CHIP. Am J Physiol Renal Physiol. 2010;299:F1462-72 pubmed publisher
    ..In conclusion, 17-AAG may represent a novel pharmacological tool to interfere with Na(+) reabsorption and hypertension. ..
  35. Palubinsky A, Stankowski J, Kale A, Codreanu S, Singer R, Liebler D, et al. CHIP Is an Essential Determinant of Neuronal Mitochondrial Stress Signaling. Antioxid Redox Signal. 2015;23:535-49 pubmed publisher
    Determine the mechanism by which C-terminus of HSC70-interacting protein (CHIP) induction alters neuronal survival under conditions of mitochondrial stress induced by oxygen glucose deprivation...
  36. Arndt V, Dick N, Tawo R, Dreiseidler M, Wenzel D, Hesse M, et al. Chaperone-assisted selective autophagy is essential for muscle maintenance. Curr Biol. 2010;20:143-8 pubmed publisher
    ..the small heat shock protein HspB8 during disposal that is initiated by the chaperone-associated ubiquitin ligase CHIP and the autophagic ubiquitin adaptor p62...
  37. 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...
  38. Le N, Takei Y, Shishido T, Woo C, Chang E, Heo K, et al. p90RSK targets the ERK5-CHIP ubiquitin E3 ligase activity in diabetic hearts and promotes cardiac apoptosis and dysfunction. Circ Res. 2012;110:536-50 pubmed publisher
    ..cardiac apoptosis after myocardial infarction (MI), especially in hyperglycemic states, via association with CHIP ubiquitin (Ub) ligase and subsequent upregulation of CHIP ligase activity, which induces ICER ubiquitination and ..
  39. Anderson L, Meeker R, Poulton W, Huang D. Brain distribution of carboxy terminus of Hsc70-interacting protein (CHIP) and its nuclear translocation in cultured cortical neurons following heat stress or oxygen-glucose deprivation. Cell Stress Chaperones. 2010;15:487-95 pubmed publisher
    Carboxy terminus of Hsc70-interacting protein (CHIP) is thought to be a cytoprotective protein with protein quality control roles in neurodegenerative diseases and myocardial ischemia...
  40. Daviau A, Proulx R, Robitaille K, Di Fruscio M, Tanguay R, Landry J, et al. Down-regulation of the mixed-lineage dual leucine zipper-bearing kinase by heat shock protein 70 and its co-chaperone CHIP. J Biol Chem. 2006;281:31467-77 pubmed
    ..Interestingly, the Hsp70 co-chaperone CHIP, an E3 ubiquitin ligase, seems to be indispensable for this process since Hsp70 failed to induce DLK degradation in ..
  41. Dickey C, Koren J, Zhang Y, Xu Y, Jinwal U, Birnbaum M, et al. Akt and CHIP coregulate tau degradation through coordinated interactions. Proc Natl Acad Sci U S A. 2008;105:3622-7 pubmed publisher
    ..During stress, Akt is ubiquitinated and degraded by the tau ubiquitin ligase CHIP, and this largely depends on the Hsp90 complex...
  42. Centrone M, Ranieri M, Di Mise A, Berlingerio S, Russo A, Deen P, et al. AQP2 Abundance is Regulated by the E3-Ligase CHIP Via HSP70. Cell Physiol Biochem. 2017;44:515-531 pubmed publisher
    ..Here, we investigated the potential role of the CHIP E3 ligase in AQP2 regulation...
  43. Reventun P, Alique M, Cuadrado I, Marquez S, Toro R, Zaragoza C, et al. iNOS-Derived Nitric Oxide Induces Integrin-Linked Kinase Endocytic Lysosome-Mediated Degradation in the Vascular Endothelium. Arterioscler Thromb Vasc Biol. 2017;37:1272-1281 pubmed publisher
    ..Mechanistically, NO increased ILK ubiquitination mediated by the E3 ubiquitin ligase CHIP (C terminus of HSC70-interacting protein), but ILK ubiquitination was not followed by proteasome degradation...
  44. 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...
  45. Xue F, Wu Y, Zhao X, Zhao T, Meng Y, Zhao Z, et al. CHIP mediates down-regulation of nucleobindin-1 in preosteoblast cell line models. Cell Signal. 2016;28:1058-65 pubmed publisher
    ..HA-CHIP over-expressed and endogenous CHIP depleted MC3T3-E1 stable cell lines, identifying NUCB1 as a novel CHIP/Stub1 targeted protein...
  46. Millson S, Vaughan C, Zhai C, Ali M, Panaretou B, Piper P, et al. Chaperone ligand-discrimination by the TPR-domain protein Tah1. Biochem J. 2008;413:261-8 pubmed publisher
    ..In the present study we also show that Tah1 can affect the ATPase activity of Hsp90, in common with some other TPR-domain proteins. ..
  47. Sisoula C, Gonos E. CHIP E3 ligase regulates mammalian senescence by modulating the levels of oxidized proteins. Mech Ageing Dev. 2011;132:269-72 pubmed publisher
    Senescence can be induced by various stressors including oxidative stress. It has been reported that CHIP (C-terminus of Hsp70-interacting protein) ligase is induced during senescence while CHIP(-/-) mice exhibit accelerated aging...
  48. Ronnebaum S, Wu Y, McDonough H, Patterson C. The ubiquitin ligase CHIP prevents SirT6 degradation through noncanonical ubiquitination. Mol Cell Biol. 2013;33:4461-72 pubmed publisher
    The ubiquitin ligase CHIP (carboxyl terminus of Hsp70-interacting protein) regulates protein quality control, and CHIP deletion accelerates aging and reduces the life span in mice...
  49. Cook C, Gendron T, Scheffel K, Carlomagno Y, Dunmore J, Deture M, et al. Loss of HDAC6, a novel CHIP substrate, alleviates abnormal tau accumulation. Hum Mol Genet. 2012;21:2936-45 pubmed publisher
    ..The ubiquitin ligase carboxy terminus of Hsp70-interacting protein (CHIP) and the molecular chaperone Hsp90 are implicated in protein triage decisions involving tau, and have consequently ..
  50. Shi C, Huang X, Zhang B, Zhu D, Luo H, Lu Q, et al. The Inhibition of Heat Shock Protein 90 Facilitates the Degradation of Poly-Alanine Expanded Poly (A) Binding Protein Nuclear 1 via the Carboxyl Terminus of Heat Shock Protein 70-Interacting Protein. PLoS ONE. 2015;10:e0138936 pubmed publisher increase in the interaction of PABPN1 with the carboxyl terminus of heat shock protein 70-interacting protein (CHIP). The overexpression of CHIP suppressed the aggregation of mutant PABPN1 in transfected cells...
  51. Zhao Y, Guo H, Qiao G, Zucker M, Langdon W, Zhang J. E3 Ubiquitin Ligase Cbl-b Regulates Thymic-Derived CD4+CD25+ Regulatory T Cell Development by Targeting Foxp3 for Ubiquitination. J Immunol. 2015;194:1639-45 pubmed publisher
    ..Mechanistically, Cbl-b binds to Foxp3 upon TCR stimulation and, together with Stub1, targets Foxp3 for ubiquitination and subsequently degradation in the proteasome...
  52. Choi Y, Jeong D, Lee J, Yoo S. Regulation of fragile X mental retardation 1 protein by C-terminus of Hsc70-interacting protein depends on its phosphorylation status. Biochem Biophys Res Commun. 2014;453:192-7 pubmed publisher
    ..Expression of FMR1 inversely correlated with expression of the C-terminus of Hsc70-interacting protein (CHIP) and, based on the known activity of CHIP in protein homeostasis, we suggest that CHIP regulates expression of FMR1...
  53. 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...
  54. WILLIAMS A, Knutson T, Colomer Gould V, Paulson H. In vivo suppression of polyglutamine neurotoxicity by C-terminus of Hsp70-interacting protein (CHIP) supports an aggregation model of pathogenesis. Neurobiol Dis. 2009;33:342-53 pubmed publisher
    ..Here we provide evidence that the co-chaperone and ubiquitin ligase, CHIP (C-terminus of Hsp70-interacting protein), is a central component to the homeostatic mechanisms countering toxic ..
  55. Jiang B, Shen H, Chen Z, Yin L, Zan L, Rui L. Carboxyl terminus of HSC70-interacting protein (CHIP) down-regulates NF-κB-inducing kinase (NIK) and suppresses NIK-induced liver injury. J Biol Chem. 2015;290:11704-14 pubmed publisher
    ..Here we identified CHIP (carboxyl terminus of HSC70-interacting protein) as a new negative regulator of NIK...
  56. 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...
  57. 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-..
  58. Schisler J, Rubel C, Zhang C, Lockyer P, Cyr D, Patterson C. CHIP protects against cardiac pressure overload through regulation of AMPK. J Clin Invest. 2013;123:3588-99 pubmed publisher
    ..Here we demonstrate that C terminus of HSC70-interacting protein (CHIP), a regulator of protein quality control, influences the metabolic response to pressure overload by direct ..
  59. Xie J, Gu J. Identification of C-terminal Hsp70-interacting protein as a mediator of tumour necrosis factor action in osteoblast differentiation by targeting osterix for degradation. J Cell Mol Med. 2015;19:1814-24 pubmed publisher
    ..The purpose of this study was to test that C terminus of Hsc70-interacting protein (CHIP) has a specific role in suppressing the osteogenic activity of osteoblasts under inflammatory conditions...
  60. Willis M, Min J, Wang S, McDonough H, Lockyer P, Wadosky K, et al. Carboxyl terminus of Hsp70-interacting protein (CHIP) is required to modulate cardiac hypertrophy and attenuate autophagy during exercise. Cell Biochem Funct. 2013;31:724-35 pubmed publisher
    The carboxyl terminus of Hsp70-interacting protein (CHIP) is a ubiquitin ligase/cochaperone critical for the maintenance of cardiac function...
  61. 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
    ..cytokines and lipopolysaccharides lead to the degradation of Foxp3 through the action of the E3 ubiquitin ligase Stub1. Stub1 interacted with Foxp3 to promote its K48-linked polyubiquitination in an Hsp70-dependent manner...
  62. 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
    ..a family with two of three siblings afflicted with ataxia and hypogonadism and identified a homozygous mutation in STUB1 (NM_005861) c.737C?T, p.Thr246Met, a gene that encodes the protein CHIP (C-terminus of HSC70-interacting protein)...
  63. Seo J, Lee E, Sung H, Seong D, Dondelinger Y, Shin J, et al. CHIP controls necroptosis through ubiquitylation- and lysosome-dependent degradation of RIPK3. Nat Cell Biol. 2016;18:291-302 pubmed publisher
    ..expression level is negatively regulated by CHIP (carboxyl terminus of Hsp70-interacting protein; also known as STUB1) E3 ligase-mediated ubiquitylation...
  64. Zhou Y, Zhu Y, Zhang L, Wu T, Wu T, Zhang W, et al. Human Stem Cells Overexpressing miR-21 Promote Angiogenesis in Critical Limb Ischemia by Targeting CHIP to Enhance HIF-1α Activity. Stem Cells. 2016;34:924-34 pubmed publisher
    ..Furthermore, carboxyl terminus of Hsc70-interacting protein (CHIP) was found to be the target gene for miR-21-mediated activation of hypoxia-inducible factor 1α (HIF-1α) in ..
  65. Chen L, Kong X, Fu J, Xu Y, Fang S, Hua P, et al. CHIP facilitates ubiquitination of inducible nitric oxide synthase and promotes its proteasomal degradation. Cell Immunol. 2009;258:38-43 pubmed publisher
    ..In this study, we showed that iNOS was ubiquitinated and degraded dependent on CHIP (COOH terminus of heat shock protein 70-interacting protein), a chaperone-dependent ubiquitin ligase...
  66. Kim C, Yun N, Lee J, Youdim M, Ju C, Kim W, et al. Phosphorylation of CHIP at Ser20 by Cdk5 promotes tAIF-mediated neuronal death. Cell Death Differ. 2016;23:333-46 pubmed publisher
    ..Likewise, C-terminus of Hsc70-interacting protein (CHIP) is linked to neurological disorders, serving as an E3 ubiquitin ligase for targeting damaged or toxic proteins for ..
  67. Yoshida K, Watanabe M, Hatakeyama S. ZNRF1 interacts with tubulin and regulates cell morphogenesis. Biochem Biophys Res Commun. 2009;389:506-11 pubmed publisher
    ..These results suggest that ZNRF1 mediates regulation of neuritogenesis via interaction with tubulin. ..
  68. Yang K, Zhang T, Tian C, Jia L, Du J, Li H. Carboxyl terminus of heat shock protein 70-interacting protein inhibits angiotensin II-induced cardiac remodeling. Am J Hypertens. 2012;25:994-1001 pubmed publisher
    The carboxyl terminus of heat shock protein 70-interacting protein (CHIP), an E3 ligase/chaperone, was found to protect cardiomyocytes against apoptosis induced by ischemic injury; however, the functional role of CHIP in remodeling ..
  69. Su C, Lan K, Li C, Chao Y, Lin H, Lee S, et al. Phosphorylation accelerates geldanamycin-induced Akt degradation. Arch Biochem Biophys. 2013;536:6-11 pubmed publisher
    ..In this report, we show that GA-mediated transient activation of Akt accelerates its association with the E3 ligase CHIP (C-terminal Hsp70-interacting protein)-mediated ubiquitination and subsequent proteasome degradation.