1. CSNAP, the smallest CSN subunit, modulates proteostasis through cullin-RING ubiquitin ligases.
- Author
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Füzesi-Levi MG, Fainer I, Ivanov Enchev R, Ben-Nissan G, Levin Y, Kupervaser M, Friedlander G, Salame TM, Nevo R, Peter M, and Sharon M
- Subjects
- Cell Cycle radiation effects, Cell Line, Cell Survival radiation effects, DNA Repair radiation effects, Humans, Models, Biological, Protein Binding radiation effects, Proteome metabolism, Ultraviolet Rays, Cullin Proteins metabolism, Intercellular Signaling Peptides and Proteins metabolism, Protein Subunits metabolism, Proteostasis radiation effects, Ubiquitin-Protein Ligases metabolism
- Abstract
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.
- Published
- 2020
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