Rig-G negatively regulates SCF-E3 ligase activities by disrupting the assembly of COP9 signalosome complex.
Biochem Biophys Res Commun
; 432(3): 425-30, 2013 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-23415865
ABSTRACT
We previously showed that Rig-G, an antiproliferative protein induced by interferon, can sequester CSN5 protein in the cytoplasm. Here, we report that Rig-G can destroy the functions of CSN5-containing COP9 signalosome (CSN), a highly conserved multiprotein complex implicated in protein deneddylation, deubiquitination, and phosphorylation. By damaging integrity and stability of the CSN complex, Rig-G can dramatically reduce the cellular content of CSN complex and inhibit its regulatory roles in assembly and activation of cullin-RING ubiquitin E3 ligases (CRL). Furthermore, Rig-G can cause excessive activation of CRL through inhibition of CSN-mediated deneddylation, largely decreasing protein levels of Cul1 and ßTrCP, two important subunits of SCF (Skp1-Cul1-F-box protein)-E3 ligase. Rig-G can also attenuate the ability of CSN to recruit USP15 and impair CSN-associated deubiquitination. Increased autoubiquitination of ßTrCP and concomitant accumulation of target substrates (such as IκBα) are observed in Rig-G-expressing cells. Taken together, our findings reveal for the first time the negative regulation of Rig-G on SCF-E3 ligase activities through disrupting CSN complex, not only contributing to further investigation on biological functions of Rig-G, but also leading to better understanding of the CSN complex as a potential target in tumor diagnosis and treatment.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeo Hidrolases
/
Proteínas Ligases SKP Culina F-Box
/
Complexos Multiproteicos
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Peptídeos e Proteínas de Sinalização Intracelular
Limite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
China