COP9 signalosome function in the DDR

FEBS Lett. 2011 Sep 16;585(18):2845-52. doi: 10.1016/j.febslet.2011.04.027. Epub 2011 Apr 16.

Abstract

The COP9 signalosome (CSN) is a platform for protein communication in eukaryotic cells. It has an intrinsic metalloprotease that removes the ubiquitin (Ub)-like protein Nedd8 from cullins. CSN-mediated deneddylation regulates culling-RING Ub ligases (CRLs) and controls ubiquitination of proteins involved in DNA damage response (DDR). CSN forms complexes with CRLs containing cullin 4 (CRL4s) which act on chromatin playing crucial roles in DNA repair, checkpoint control and chromatin remodeling. Furthermore, via associated kinases the CSN controls the stability of DDR effectors such as p53 and p27 and thereby the DDR outcome. DDR is a protection against cancer and deregulation of CSN function causes cancer making it an attractive pharmacological target. Here we review current knowledge on CSN function in DDR.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • COP9 Signalosome Complex
  • DNA Damage*
  • DNA Repair*
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Multiprotein Complexes / metabolism*
  • Neoplasms / metabolism
  • Peptide Hydrolases / metabolism*
  • Phosphorylation
  • Ubiquitination

Substances

  • Intracellular Signaling Peptides and Proteins
  • Multiprotein Complexes
  • Peptide Hydrolases
  • COPS5 protein, human
  • COP9 Signalosome Complex