E3 ubiquitin-protein ligase CHIP (CHIP (Carboxyl terminus of Hsc70-interacting protein))

E3 ubiquitin-protein ligase CHIP (STUB1) is a quality-control E3 ligase that selectively ubiquitylates unfolded or misfolded proteins by collaborating with molecular chaperones such as Hsp90 and Hsc70/Hsp70. It contains a U-box domain that is essential for its ubiquitin ligase activity. CHIP functions at the intersection of protein folding and degradation pathways, playing a crucial role in maintaining cellular protein homeostasis. It enhances HSP70 induction during acute stress and mediates its turnover during stress recovery. Beyond protein quality control, CHIP regulates various cellular processes including cell cycle progression through p21 degradation. Its expression is altered in multiple cancers, with context-dependent effects on prognosis. Mutations in the STUB1 gene are associated with spinocerebellar ataxia type 16, highlighting its importance in neurological function.

Other names

STUB1 (STIP1 Homology And U-Box Containing Protein 1)CHIPHSPABP2 (Heat shock protein A binding protein 2)NY-CO-7SDCCAG7UBOX1LA16c-313D11.6

Collaborates with molecular chaperones (Hsp90, Hsc70, Hsp70) to selectively ubiquitylate denatured/misfolded proteins. Binds to and inhibits the ATPase activity of HSC70 and HSP70. Blocks the forward reaction of the HSC70-HSP70 substrate-binding cycle. Promotes ubiquitylation of chaperone-bound misfolded proteins.