title: CSNAP Is a Stoichiometric Subunit of the COP9 Signalosome.
abstract: 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.
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Shelly
authors.initials: S
authors.lastname: Rozen
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Füzesi-Levi
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Gili
authors.initials: G
authors.lastname: Ben-Nissan
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Limor
authors.initials: L
authors.lastname: Mizrachi
authors.affiliation: The Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gabashvili
authors.affiliation: The Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Yishai
authors.initials: Y
authors.lastname: Levin
authors.affiliation: Biological Services Unit, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Shifra
authors.initials: S
authors.lastname: Ben-Dor
authors.affiliation: Chemical Research Support, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Miriam
authors.initials: M
authors.lastname: Eisenstein
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 7610001, Israel. Electronic address: michal.sharon@weizmann.ac.il.
authors.forename: Michal
authors.initials: M
authors.lastname: Sharon
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D000075686:COP9 Signalosome Complex; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D010447:Peptide Hydrolases / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism; D055503:Protein Multimerization
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C470634:COPS6 protein, human; C000609535:COPS9 protein, human; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D011494:Protein Kinases; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex