UV-dependent phosphorylation of COP9/signalosome in UV-induced apoptosis

Dubois,Emilie  Laure; Gerber,Scott; Kisselev,Alexei; Harel-Bellan,Annick; Groisman,Regina

doi:10.3892/or.2016.4671

UV-dependent phosphorylation of COP9/signalosome in UV-induced apoptosis

Authors:
- Emilie Laure Dubois
- Scott Gerber
- Alexei Kisselev
- Annick Harel-Bellan
- Regina Groisman
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Affiliations: Institute for Integrative Biology of the Cell (I2BC), IBITECS, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, 91198 Gif-sur-Yvette Cedex, France, Norris Cotton Cancer Center, Lebanon, NH 03756, USA
Published online on: March 11, 2016 https://doi.org/10.3892/or.2016.4671
Pages: 3101-3105

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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.

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