@article{ad84d709394d4460a247084d96e31c06,
title = "CSNAP, the smallest CSN subunit, modulates proteostasis through cullin-RING ubiquitin ligases",
abstract = "The cullin-RING ubiquitin E3 ligase (CRL) family consists of similar to 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.",
author = "Fuzesi-Levi, {Maria G.} and Irit Fainer and Enchev, {Radoslav Ivanov} and Gili Ben-Nissan and Yishai Levin and Meital Kupervaser and Salame, {Tomer Meir} and Reinat Nevo and Matthias Peter and Michal Sharon",
note = "We thank Dieter A. Wolf for comments on the paper, and Dr. Ron Rotkopf for the statistical analysis. MS is grateful for the financial support of the US National Institutes of Health, grant no. GM121834 and for an Israel Science Foundation (ISF) grant 300/17. MS is the incumbent of the Aharon and Ephraim Katzir Memorial Professorial Chair. GF is the Incumbent of the David and Stacey Cynamon Research fellow Chair in Genetics and Personalized Medicine MGF-L, GB-N, RIE, MP and MS designed the experiments and analyzed the data. MGF-L and IF performed the cell biology and biochemistry experiments. MGF-L and TMS performed the flow cytometry, and MGF-L and RN performed the microscopy experiments. GB-N performed the mass spectrometry and RIE the Kd measurement experiments. YL and MK performed the SILAC and label-free proteomics analysis. GF performed the bioinformatics analysis of the proteomics data. MGF-L, GB-N and MS wrote the paper.",
year = "2020",
month = mar,
doi = "10.1101/433532v1",
language = "الإنجليزيّة",
volume = "27",
pages = "984--998",
journal = "Cell Death and Differentiation",
issn = "1350-9047",
publisher = "Springer Nature",
number = "3",
}