HSC70 coordinates COP9 signalosome and SCF ubiquitin ligase activity to enable a prompt stress response.

ABSTRACT: The SCF (SKP1/CUL1/F-box protein) ubiquitin ligase complex plays a protective role against external stress, such as ultraviolet irradiation. The emergence of substrates activates SCF through neddylation, the covalent attachment of ubiquitin-like protein NEDD8 to CUL1. After substrate degradation, SCF is inactivated through deneddylation by COP9-signalosome (CSN), a solo enzyme that can deneddylate SCF. How the activity of CSN and SCF is coordinated within the cell is not fully understood. Here, we find that heat-shock cognate 70 (HSC70) chaperone coordinates SCF and CSN activation dependent on the neddylation status and substrate availability. Under basal conditions and low substrate availability, HCS70 directly enhances CSN deneddylation activity, thereby reducing SCF activity. Under SCF-

SUBMITTER: Nishimura S 

PROVIDER: S-EPMC11894141 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature