Gene Symbol: Stub1
Description: STIP1 homology and U-box containing protein 1
Alias: Chip, E3 ubiquitin-protein ligase CHIP, STIP1 homology and U-box containing protein 1, E3 ubiquitin protein ligase, carboxy terminus of Hsp70-interacting protein
Species: rat
Products:     Stub1

Top Publications

  1. 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...
  2. 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...
  3. Li F, Xie P, Fan Y, Zhang H, Zheng L, Gu D, et al. C terminus of Hsc70-interacting protein promotes smooth muscle cell proliferation and survival through ubiquitin-mediated degradation of FoxO1. J Biol Chem. 2009;284:20090-8 pubmed publisher
    ..Here we showed that overexpression of C terminus of Hsc70-interacting protein (CHIP) promoted ubiquitination and degradation of FoxO1 in SMCs in response to tumor necrosis factor-alpha...
  4. 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-..
  5. Han W, Chen L, Liu J, Guo A. Enhanced tenogenic differentiation and tendon-like tissue formation by CHIP overexpression in tendon-derived stem cells. Acta Biochim Biophys Sin (Shanghai). 2017;49:311-317 pubmed publisher
    The carboxyl terminus of Hsc70-interacting protein (CHIP, also known as STUB1) plays critical roles in the proliferation and differentiation of many types of cells...
  6. Massinen S, Tammimies K, Tapia Paez I, Matsson H, Hokkanen M, Söderberg O, et al. Functional interaction of DYX1C1 with estrogen receptors suggests involvement of hormonal pathways in dyslexia. Hum Mol Genet. 2009;18:2802-12 pubmed publisher
    ..As DYX1C1 was suggested to interact with the U-box protein CHIP (carboxy terminus of Hsc70-interacting protein), which also participates in the degradation of estrogen receptors ..
  7. 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...
  8. Sarparanta J, Jonson P, Golzio C, Sandell S, Luque H, Screen M, et al. Mutations affecting the cytoplasmic functions of the co-chaperone DNAJB6 cause limb-girdle muscular dystrophy. Nat Genet. 2012;44:450-5, S1-2 pubmed publisher
  9. Wang Q, Song F, Zhang C, Zhao X, Zhu Z, Yu S, et al. Carboxyl-terminus of Hsc70 interacting protein mediates 2,5-hexanedione-induced neurofilament medium chain degradation. Biochem Pharmacol. 2011;81:793-9 pubmed publisher
    ..We first demonstrated that the E3 ligase carboxyl-terminus of Hsc70 interacting protein (CHIP), originally identified as a co-chaperone of Hsc70, directly interacted with NFs medium chain (NF-M) and then ..

More Information


  1. 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 ..
  2. Peng H, Morishima Y, Jenkins G, Dunbar A, Lau M, Patterson C, et al. Ubiquitylation of neuronal nitric-oxide synthase by CHIP, a chaperone-dependent E3 ligase. J Biol Chem. 2004;279:52970-7 pubmed
    ..In the current study, we have examined whether CHIP, a chaperone-dependent E3 ubiquitin-protein isopeptide ligase that is known to ubiquitylate other hsp90-chaperoned ..
  3. 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...
  4. 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...
  5. 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. ..
  6. Parsons J, Tait P, Finch D, Dianova I, Edelmann M, Khoronenkova S, et al. Ubiquitin ligase ARF-BP1/Mule modulates base excision repair. EMBO J. 2009;28:3207-15 pubmed publisher
    ..Our findings provide a novel mechanism regulating steady-state levels of BER proteins. ..
  7. Zhang Q, Han D, Wang R, Dong Y, Yang F, Vadlamudi R, et al. C terminus of Hsc70-interacting protein (CHIP)-mediated degradation of hippocampal estrogen receptor-alpha and the critical period hypothesis of estrogen neuroprotection. Proc Natl Acad Sci U S A. 2011;108:E617-24 pubmed publisher
    ..interaction with the E3 ubiquitin ligase C terminus of heat shock cognate protein 70 (Hsc70)-interacting protein (CHIP) that leads to its ubiquitination/proteasomal degradation following LTED (10-wk ovariectomy)...
  8. 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 ..
  9. Ashida H, Maeda Y, Kinoshita T. DPM1, the catalytic subunit of dolichol-phosphate mannose synthase, is tethered to and stabilized on the endoplasmic reticulum membrane by DPM3. J Biol Chem. 2006;281:896-904 pubmed
    ..Free DPM1 was strongly associated with the C terminus of Hsc70-interacting protein (CHIP), a chaperone-dependent E3 ubiquitin ligase, suggesting that DPM1 is ubiquitinated, at least in part, by CHIP.
  10. 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
    ..For the screening of valosin-containing protein, carboxyl terminus of Hsp70-interacting protein (CHIP), and amphiphysin II interaction partners, we utilized a membrane-based array technology that allows the ..
  11. 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 ..
  12. Gil Lorenzo A, Costantino V, Appiolaza M, Cacciamani V, Benardon M, Bocanegra V, et al. Heat Shock Protein 70 and CHIP Promote Nox4 Ubiquitination and Degradation within the Losartan Antioxidative Effect in Proximal Tubule Cells. Cell Physiol Biochem. 2015;36:2183-97 pubmed publisher
    ..Hsp70 regulates a diverse set of signaling pathways through their interactions with proteins. CHIP is a E3 ubiquitin ligase that targets proteins for polyubiquitination and degradation...
  13. Pabarcus M, Hoe N, Sadeghi S, Patterson C, Wiertz E, Correia M. CYP3A4 ubiquitination by gp78 (the tumor autocrine motility factor receptor, AMFR) and CHIP E3 ligases. Arch Biochem Biophys. 2009;483:66-74 pubmed publisher
    ..polytopic RING-finger E3, effectively ubiquitinated CYP3A4 in vitro, as did the UbcH5a-dependent cytosolic E3 CHIP. CYP3A4 immunoprecipitation coupled with anti-Ub immunoblotting analyses confirmed its ubiquitination in these ..
  14. Lim M, Kawamura T, Ohsawa Y, Ohtsubo M, Asakawa S, Takayanagi A, et al. Parkin interacts with LIM Kinase 1 and reduces its cofilin-phosphorylation activity via ubiquitination. Exp Cell Res. 2007;313:2858-74 pubmed
    ..LIMK1 also interacted with previously known parkin interactors Hsp70 and CHIP. Parkin enhanced LIMK1-ubiquitination in the human neuroblastoma-derived BE(2)-M17 cell line, but not in the human ..
  15. 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...
  16. 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...
  17. Kim S, Acharya P, Engel J, Correia M. Liver cytochrome P450 3A ubiquitination in vivo by gp78/autocrine motility factor receptor and C terminus of Hsp70-interacting protein (CHIP) E3 ubiquitin ligases: physiological and pharmacological relevance. J Biol Chem. 2010;285:35866-77 pubmed publisher
    ..ubiquitinated in vivo, and in vitro studies have identified the ER-integral gp78 and the cytosolic co-chaperone, CHIP (C terminus of Hsp70-interacting protein), as the relevant E3 Ub-ligases, along with their cognate E2 Ub-..
  18. 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) ..
  19. Shi R, Wang S, Qi X, Chen S, Chen P, Zhang Q. Lose dose genistein inhibits glucocorticoid receptor and ischemic brain injury in female rats. Neurochem Int. 2014;65:14-22 pubmed publisher
  20. Singh A, Pati U. CHIP stabilizes amyloid precursor protein via proteasomal degradation and p53-mediated trans-repression of β-secretase. Aging Cell. 2015;14:595-604 pubmed publisher
    ..We have shown that both in neurons and in HEK-APP cells, BACE1 is a new substrate of E3-ligase CHIP and an inverse relation exists between CHIP and BACE1 level...
  21. Peng X, Guo X, Borkan S, Bharti A, Kuramochi Y, Calderwood S, et al. Heat shock protein 90 stabilization of ErbB2 expression is disrupted by ATP depletion in myocytes. J Biol Chem. 2005;280:13148-52 pubmed
  22. 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...
  23. Xiong W, Liu S, Cai W, Wen J, Fu Y, Peng J, et al. The carboxyl terminus of heat shock protein 70-interacting protein (CHIP) participates in high glucose-induced cardiac injury. Free Radic Biol Med. 2017;106:339-344 pubmed publisher
    The carboxyl terminus of heat shock protein 70-interacting protein (CHIP) is confirmed to have a protective effect on the myocardium, but its effect on diabetic cardiomyopathy is unclear...
  24. 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)...
  25. Carrettiero D, Hernandez I, Neveu P, Papagiannakopoulos T, Kosik K. The cochaperone BAG2 sweeps paired helical filament- insoluble tau from the microtubule. J Neurosci. 2009;29:2151-61 pubmed publisher
    ..The components of a Tau protein triage system consisting of CHIP/Hsp70 and other chaperones have begun to emerge...
  26. Lee H, Sengupta N, Villagra A, Rezai Zadeh N, Seto E. Histone deacetylase 8 safeguards the human ever-shorter telomeres 1B (hEST1B) protein from ubiquitin-mediated degradation. Mol Cell Biol. 2006;26:5259-69 pubmed
    ..Phosphorylated HDAC8 preferentially recruits Hsp70 to a complex that inhibits the CHIP (C-terminal heat shock protein interacting protein) E3 ligase-mediated degradation of hEST1B...
  27. Mezghenna K, Leroy J, Azay Milhau J, Tousch D, Castex F, Gervais S, et al. Counteracting neuronal nitric oxide synthase proteasomal degradation improves glucose transport in insulin-resistant skeletal muscle from Zucker fa/fa rats. Diabetologia. 2014;57:177-86 pubmed publisher
    ..nNOS with the chaperone heat-shock protein 70 and the co-chaperone, carboxyl terminus of Hsc70-interacting protein (CHIP). In addition, an alteration in nNOS sarcolemmal localisation was observed...
  28. Shang Y, Xu X, Duan X, Guo J, Wang Y, Ren F, et al. Hsp70 and Hsp90 oppositely regulate TGF-? signaling through CHIP/Stub1. Biochem Biophys Res Commun. 2014;446:387-92 pubmed publisher
    ..We previously reported that E3 ubiquitin ligase CHIP (carboxyl terminus of Hsc70-interacting protein, also named Stub1) controlled the sensitivity of TGF-? signaling by modulating the basal level of Smad3 through ubiquitin-mediated ..
  29. Dimant H, Zhu L, Kibuuka L, Fan Z, Hyman B, McLean P. Direct visualization of CHIP-mediated degradation of alpha-synuclein in vivo: implications for PD therapeutics. PLoS ONE. 2014;9:e92098 pubmed publisher
    ..Here we use a gene therapy approach to evaluate the applicability of the Hsp70 co-chaperone CHIP (C-terminal Hsp70 interacting protein) as a therapeutic candidate and examine its direct effect on alpha synuclein ..
  30. 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...
  31. Xie P, Fan Y, Zhang H, Zhang Y, She M, Gu D, et al. CHIP represses myocardin-induced smooth muscle cell differentiation via ubiquitin-mediated proteasomal degradation. Mol Cell Biol. 2009;29:2398-408 pubmed publisher
    ..Here we show that the E3 ligase C terminus of Hsc70-interacting protein (CHIP) represses myocardin-dependent SMC gene expression and transcriptional activity...
  32. Zhang Y, Xu Y, Liu X, Li D, Yin J, Liu Y, et al. Carboxyl terminus of heat-shock cognate 70-interacting protein degrades tau regardless its phosphorylation status without affecting the spatial memory of the rats. J Neural Transm (Vienna). 2008;115:483-91 pubmed publisher
    ..Recently, it has been reported that carboxyl terminus of Hsc70-interacting protein (CHIP) is the specific tau E3 ligase and it mediates tau degradation in vitro...
  33. Zhao B, Sun G, Feng G, Duan W, Zhu X, Chen S, et al. Carboxy terminus of heat shock protein (HSP) 70-interacting protein (CHIP) inhibits HSP70 in the heart. J Physiol Biochem. 2012;68:485-91 pubmed publisher
    ..The levels of HSP70 and carboxy terminus of HSP70-interacting protein (CHIP) in the heart tissue were assessed by enzyme-linked immunosorbent assay (ELISA) and Western blotting...