CRL4^AMBRA1 targets Elongin C for ubiquitination and degradation to modulate CRL5 signaling.

ABSTRACT: Multi-subunit cullin-RING ligases (CRLs) are the largest family of ubiquitin E3 ligases in humans. CRL activity is tightly regulated to prevent unintended substrate degradation or autocatalytic degradation of CRL subunits. Using a proteomics strategy, we discovered that CRL4^AMBRA1 (CRL substrate receptor denoted in superscript) targets Elongin C (ELOC), the essential adapter protein of CRL5 complexes, for polyubiquitination and degradation. We showed that the ubiquitin ligase function of CRL4^AMBRA1 is required to disrupt the assembly and attenuate the ligase activity of human CRL5^SOCS3 and HIV-1 CRL5^VIF complexes as AMBRA1 depletion leads to hyperactivation of both CRL5 complexes. Moreover, CRL4^AMBRA

SUBMITTER: Chen SH 

PROVIDER: S-EPMC6138441 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature