Rig-G negatively regulates SCF-E3 ligase activities by disrupting the assembly of COP9 signalosome complex
| Autor: | Zhang-Lin Zhang, Gui-Ping Xu, Di Xia, Shu Xiao, Qing-Ping Zou, Pei-Min Jia, Jian-Hua Tong, Li-Kun Zhuang |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
viruses
Biophysics Biochemistry Protein deneddylation Ubiquitin Cell Line Tumor Humans COP9 signalosome Molecular Biology chemistry.chemical_classification DNA ligase SKP Cullin F-Box Protein Ligases biology COP9 Signalosome Complex fungi Intracellular Signaling Peptides and Proteins Ubiquitination food and beverages Cell Biology Cullin Proteins Ubiquitin ligase Cell biology chemistry Multiprotein Complexes biology.protein CUL1 Peptide Hydrolases Deubiquitination |
| Zdroj: | Biochemical and Biophysical Research Communications. 432:425-430 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2013.01.132 |
| Popis: | 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 βTrCP, 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 βTrCP 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. |
| Databáze: | OpenAIRE |
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