title: CIF-1, a shared subunit of the COP9/signalosome and eukaryotic initiation factor 3 complexes, regulates MEL-26 levels in the Caenorhabditis elegans embryo.
abstract: The COP9/signalosome (CSN) is an evolutionarily conserved macromolecular complex that regulates the cullin-RING ligase (CRL) class of E3 ubiquitin ligases, primarily by removing the ubiquitin-like protein Nedd8 from the cullin subunit. In the Caenorhabditis elegans embryo, the CSN controls the degradation of the microtubule-severing protein MEI-1 through CUL-3 deneddylation. However, the molecular mechanisms of CSN function and its subunit composition remain to be elucidated. Here, using a proteomic approach, we have characterized the CSN and CUL-3 complexes from C. elegans embryos. We show that the CSN physically interacts with the CUL-3-based CRL and regulates its activity by counteracting the autocatalytic instability of the substrate-specific adaptor MEL-26. Importantly, we identified the uncharacterized protein K08F11.3/CIF-1 (for CSN-eukaryotic initiation factor 3 [eIF3]) as a stoichiometric and functionally important subunit of the CSN complex. CIF-1 appears to be the only ortholog of Csn7 encoded by the C. elegans genome, but it also exhibits extensive sequence similarity to eIF3m family members, which are required for the initiation of protein translation. Indeed, CIF-1 binds eIF-3.F and inactivation of cif-1 impairs translation in vivo. Taken together, our results indicate that CIF-1 is a shared subunit of the CSN and eIF3 complexes and may therefore link protein translation and degradation.
authors.affiliation: Swiss Federal Institute of Technology, Zurich, Institute of Biochemistry, Zurich, Switzerland.
authors.forename: Sarah
authors.initials: S
authors.lastname: Luke-Glaser
authors.forename: Marcia
authors.initials: M
authors.lastname: Roy
authors.forename: Brett
authors.initials: B
authors.lastname: Larsen
authors.forename: Thierry
authors.initials: T
authors.lastname: Le Bihan
authors.forename: Pavel
authors.initials: P
authors.lastname: Metalnikov
authors.forename: Mike
authors.initials: M
authors.lastname: Tyers
authors.forename: Matthias
authors.initials: M
authors.lastname: Peter
authors.forename: Lionel
authors.initials: L
authors.lastname: Pintard
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D000075686:COP9 Signalosome Complex; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian; D039621:Eukaryotic Initiation Factor-3 / Q000737:chemistry / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D008954:Models, Biological; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry; D040901:Proteomics / Q000379:methods; D034622:RNA Interference; D017386:Sequence Homology, Amino Acid; D020798:Two-Hybrid System Techniques
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D029742:Caenorhabditis elegans Proteins; D039621:Eukaryotic Initiation Factor-3; C114960:Mel-26 protein, C elegans; D046912:Multiprotein Complexes; D021122:Protein Subunits; D010447:Peptide Hydrolases; D000075686:COP9 Signalosome Complex