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CSNAP, the smallest CSN subunit, modulates proteostasis through cullin-RING ubiquitin ligases.

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.

SUBMITTER: Fuzesi-Levi MG

PROVIDER: S-EPMC7206152 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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CSNAP, the smallest CSN subunit, modulates proteostasis through cullin-RING ubiquitin ligases.

Füzesi-Levi Maria G MG Fainer Irit I Ivanov Enchev Radoslav R Ben-Nissan Gili G Levin Yishai Y Kupervaser Meital M Friedlander Gilgi G Salame Tomer Meir TM Nevo Reinat R Peter Matthias M Sharon Michal M

Cell death and differentiation 20190731 3

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 C ...[more]

PMID: 31367012

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