title: UV-dependent phosphorylation of COP9/signalosome in UV-induced apoptosis.
abstract: The COP9/signalosome (CSN) multi-protein complex regulates the activity of cullin-RING ubiquitin ligases (CRLs), including the DDB2 and CSA CRL4 ligases (CRL4DDB2 and CRL4CSA), which are involved in the repair of UV-induced DNA damages. In the present study, we demonstrated that the protein kinase ATM, a key component of the DNA damage response (DDR), phosphorylates CSN1 and CSN7a, two subunits of the CSN complex, in a UV-dependent manner. The phosphorylation of CSN1 on serine 474 was detected as early as 3 h after UV-exposure, peaked at 8 h and persisted until 48 h post-UV irradiation. Such a time course suggests a role in late DDR rather than in DNA repair. Consistently, overexpression of a phosphorylation-resistant S474A CSN1 mutant reduced UV-induced apoptosis. Thus, CSN1 appears to play a role not only in DNA repair but also in UV-induced apoptosis.
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), IBITECS, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, 91198 Gif-sur-Yvette Cedex, France.
authors.forename: Emilie Laure
authors.initials: EL
authors.lastname: Dubois
authors.affiliation: Norris Cotton Cancer Center, Lebanon, NH 03756, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Gerber
authors.affiliation: Norris Cotton Cancer Center, Lebanon, NH 03756, USA.
authors.forename: Alexei
authors.initials: A
authors.lastname: Kisselev
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), IBITECS, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, 91198 Gif-sur-Yvette Cedex, France.
authors.forename: Annick
authors.initials: A
authors.lastname: Harel-Bellan
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), IBITECS, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, 91198 Gif-sur-Yvette Cedex, France.
authors.forename: Regina
authors.initials: R
authors.lastname: Groisman
mesh_terms: D017209:Apoptosis / Q000528:radiation effects*; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D000075686:COP9 Signalosome Complex; D004249:DNA Damage; D004260:DNA Repair; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000528:radiation effects*; D014466:Ultraviolet Rays
chemical_list: C103315:GPS1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex