The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins.

摘要: To maintain quality control in cells, mechanisms distinguish among improperly folded peptides, mature and functional proteins, proteins to be targeted for degradation. The molecular chaperones, including heat-shock protein Hsp90, have the ability recognize misfolded assist their conversion a conformation. Disruption of Hsp90 heterocomplexes by inhibitor geldanamycin leads substrate degradation through ubiquitin-proteasome pathway, implicating this system triage decisions. We previously identified CHIP (carboxyl terminus Hsc70-interacting protein) an interaction partner Hsc70 (ref. 4). also interacts directly with tetratricopeptide repeat acceptor site incorporating into eliciting release regulatory cofactor p23. Here we show that abolishes steroid-binding activity transactivation potential glucocorticoid receptor, well-characterized substrate, even though it has little effect on its synthesis. Instead, induces ubiquitylation receptor proteasome. By remodelling favour degradation, modulates decisions regulate balance between folding chaperone substrates.