CRL4AMBRA1 targets Elongin C for ubiquitination and degradation to modulate CRL5 signaling.
EMBO J
; 37(18)2018 09 14.
Article
en En
| MEDLINE
| ID: mdl-30166453
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 CRL4AMBRA1 (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 CRL4AMBRA1 is required to disrupt the assembly and attenuate the ligase activity of human CRL5SOCS3 and HIV-1 CRL5VIF complexes as AMBRA1 depletion leads to hyperactivation of both CRL5 complexes. Moreover, CRL4AMBRA1 modulates interleukin-6/STAT3 signaling and HIV-1 infectivity that are regulated by CRL5SOCS3 and CRL5VIF, respectively. Thus, by discovering a substrate of CRL4AMBRA1, ELOC, the shared adapter of CRL5 ubiquitin ligases, we uncovered a novel CRL cross-regulation pathway.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Infecciones por VIH
/
VIH-1
/
Ubiquitina-Proteína Ligasas
/
Proteínas Adaptadoras Transductoras de Señales
/
Productos del Gen vif del Virus de la Inmunodeficiencia Humana
/
Ubiquitinación
/
Proteolisis
/
Elonguina
Límite:
Humans
Idioma:
En
Revista:
EMBO J
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos