TY - JOUR
T1 - CSNAP Is a Stoichiometric Subunit of the COP9 Signalosome
AU - Rozen, Shelly
AU - Fuzesi-Levi, Maria G
AU - Ben-Nissan, Gili
AU - Mizrachi, Limor
AU - Gabashvili, Alexandra
AU - Levin, Yishai
AU - Ben-Dor, Shifra
AU - Eisenstein, Miriam
AU - Sharon, Michal
N1 - We are grateful to Eitan Reuveny, Ning Wei, Yosef Shaul, and Haim Garty for providing plasmids and cells. We are thankful for the support of a Starting Grant from the European Research Council (ERC) (Horizon 2020)/ERC Grant Agreement no. 636752, an Acceleration Grant from the Israel Cancer Research Foundation, a Minerva Foundation grant, with funding from the Federal Ministry for Education and Research (Germany), and a grant from the Abisch-Frenkel Foundation (Switzerland). M.S. is the incumbent of the Elaine Blond Career Development Chair. S.R., G.B.-N., M.G.F.-L., and M.S. designed the experiments and analyzed the data. S.R., G.B.-N., M.G.F.-L. and L.M. performed the experiments. A.G., and Y.L. performed the absolute protein quantification. M.E. and S.B.-D. did the structural and bioinformatics analyses, respectively. S.R., G.B.-N., and M.S. wrote the manuscript.
PY - 2015/10/20
Y1 - 2015/10/20
N2 - The highly conserved COP9 signalosome (CSN) complex is a key regulator of all cullin-RING-ubiquitin ligases (CRLs), the largest family of E3 ubiquitin ligases. Until now, it was accepted that the CSN is composed of eight canonical components. Here, we report the discovery of an additional integral and stoichiometric subunit that had thus far evaded detection, and we named it CSNAP (CSN acidic protein). We show that CSNAP binds CSN3, CSN5, and CSN6, and its incorporation into the CSN complex is mediated through the C-terminal region involving conserved aromatic residues. Moreover, depletion of this small protein leads to reduced proliferation and a flattened and enlarged morphology. Finally, on the basis of sequence and structural properties shared by both CSNAP and DSS1, a component of the related 19S lid proteasome complex, we propose that CSNAP, the ninth CSN subunit, is the missing paralogous subunit of DSS1. The highly conserved COP9 signalosome (CSN) complex is a key regulator of all cullin-RING-ubiquitin-ligases (CRLs), the largest family of E3 ubiquitin ligases. Rozen et al. report the discovery of an additional integral and stoichiometric subunit for this highly conserved complex.
AB - The highly conserved COP9 signalosome (CSN) complex is a key regulator of all cullin-RING-ubiquitin ligases (CRLs), the largest family of E3 ubiquitin ligases. Until now, it was accepted that the CSN is composed of eight canonical components. Here, we report the discovery of an additional integral and stoichiometric subunit that had thus far evaded detection, and we named it CSNAP (CSN acidic protein). We show that CSNAP binds CSN3, CSN5, and CSN6, and its incorporation into the CSN complex is mediated through the C-terminal region involving conserved aromatic residues. Moreover, depletion of this small protein leads to reduced proliferation and a flattened and enlarged morphology. Finally, on the basis of sequence and structural properties shared by both CSNAP and DSS1, a component of the related 19S lid proteasome complex, we propose that CSNAP, the ninth CSN subunit, is the missing paralogous subunit of DSS1. The highly conserved COP9 signalosome (CSN) complex is a key regulator of all cullin-RING-ubiquitin-ligases (CRLs), the largest family of E3 ubiquitin ligases. Rozen et al. report the discovery of an additional integral and stoichiometric subunit for this highly conserved complex.
UR - http://www.scopus.com/inward/record.url?scp=84944675506&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2015.09.021
DO - 10.1016/j.celrep.2015.09.021
M3 - مقالة
SN - 2211-1247
VL - 13
SP - 585
EP - 598
JO - Cell Reports
JF - Cell Reports
IS - 3
M1 - 2073
ER -