title: CHIP: a quality-control E3 ligase collaborating with molecular chaperones.
abstract: It is notable that both the chaperone and ubiquitin-proteasome systems are required for removal of aberrant cellular proteins to ensure protein homeostasis in cells. However, the entity that links the two systems had remained elusive. Carboxyl-terminus of Hsc70 interacting protein (CHIP), originally identified as a co-chaperone of Hsc70, has both a tetratricopeptide repeat (TPR) motif and a U-box domain. The TPR motif associates with Hsc70 and Hsp90, while the U-box domain executes a ubiquitin ligase activity. Thus, CHIP is an ideal molecule acting as a protein quality-control ubiquitin ligase that selectively leads abnormal proteins recognized by molecular chaperones to degradation by the proteasome. Accumulating evidence from in vitro studies indicates that this is apparently the case. Here, we present and discuss several unresolved but critical issues related to the molecular mechanism and in vivo roles of CHIP.
authors.affiliation: Department of Molecular Oncology, Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, 113-8613, Tokyo, Japan. smurata@rinshoken.or.jp <smurata@rinshoken.or.jp>
authors.forename: Shigeo
authors.initials: S
authors.lastname: Murata
authors.forename: Tomoki
authors.initials: T
authors.lastname: Chiba
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018832:Molecular Chaperones / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D011489:Protein Denaturation; D017510:Protein Folding; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494371:HSPA8 protein, human; C494372:Hspa8 protein, mouse; D018832:Molecular Chaperones; D009097:Multienzyme Complexes; D025801:Ubiquitin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex