CSNAP, the smallest CSN subunit, modulates proteostasis through cullin-RING ubiquitin ligases
| Autor: | Gilgi Friedlander, Reinat Nevo, Radoslav I. Enchev, Tomer-Meir Salame, Yishai Levin, Irit Fainer, Maria G. Füzesi-Levi, Matthias Peter, Gili Ben-Nissan, Michal Sharon, Meital Kupervaser |
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| Jazyk: | angličtina |
| Předmět: |
0301 basic medicine
DNA Repair Proteome DNA damage Cell Survival Ultraviolet Rays Protein subunit Ubiquitin-Protein Ligases Models Biological Article Cell Line 03 medical and health sciences 0302 clinical medicine Ubiquitin Humans Molecular Biology chemistry.chemical_classification biology fungi Cell Cycle Cell Biology Cullin Proteins COP9 Signalosome Complex Ubiquitin ligase Cell biology Protein Subunits 030104 developmental biology Proteostasis Enzyme chemistry 030220 oncology & carcinogenesis biology.protein Intercellular Signaling Peptides and Proteins Cullin Protein Binding |
| Zdroj: | Cell Death & Differentiation Cell Death Differ |
| ISSN: | 1476-5403 1350-9047 |
| DOI: | 10.1038/s41418-019-0392-8 |
| Popis: | The cullin-RING ubiquitin E3 ligase (CRL) family consists of ~250 complexes that catalyze ubiquitylation of proteins to achieve cellular regulation. All CRLs are inhibited by the COP9 signalosome complex (CSN) through both enzymatic (deneddylation) and nonenzymatic (steric) mechanisms. The relative contribution of these two mechanisms is unclear. Here, we decouple the mechanisms using CSNAP, the recently discovered ninth subunit of the CSN. We find that CSNAP reduces the affinity of CSN toward CRL complexes. Removing CSNAP does not affect deneddylation, but leads to global effects on the CRL, causing altered reproductive capacity, suppressed DNA damage response, and delayed cell cycle progression. Thus, although CSNAP is only 2% of the CSN mass, it plays a critical role in the steric regulation of CRLs by the CSN. |
| Databáze: | OpenAIRE |
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