Publikationsdatum:
2018
Beschreibung:
〈p〉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〈sup〉AMBRA〈/sup〉〈sup〉1〈/sup〉 (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〈sup〉AMBRA〈/sup〉〈sup〉1〈/sup〉 is required to disrupt the assembly and attenuate the ligase activity of human CRL5〈sup〉SOCS〈/sup〉〈sup〉3〈/sup〉 and HIV-1 CRL5〈sup〉VIF〈/sup〉 complexes as AMBRA1 depletion leads to hyperactivation of both CRL5 complexes. Moreover, CRL4〈sup〉AMBRA〈/sup〉〈sup〉1〈/sup〉 modulates interleukin-6/STAT3 signaling and HIV-1 infectivity that are regulated by CRL5〈sup〉SOCS〈/sup〉〈sup〉3〈/sup〉 and CRL5〈sup〉VIF〈/sup〉, respectively. Thus, by discovering a substrate of CRL4〈sup〉AMBRA〈/sup〉〈sup〉1〈/sup〉, ELOC, the shared adapter of CRL5 ubiquitin ligases, we uncovered a novel CRL cross-regulation pathway.〈/p〉
Print ISSN:
0261-4189
Digitale ISSN:
1460-2075
Thema:
Biologie
,
Medizin
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