CSN5/Jab1 controls multiple events in the mammalian cell cycle

FEBS Lett. 2010 Nov 19;584(22):4545-52. doi: 10.1016/j.febslet.2010.10.039. Epub 2010 Oct 26.

Abstract

The COP9 signalosome (CSN) complex is critical for mammalian cell proliferation and survival, but it is not known how the CSN affects the cell cycle. In this study, MEFs lacking CSN5/Jab1 were generated using a CRE-flox system. MEFs ceased to proliferate upon elimination of CSN5/Jab1. Rescue experiments indicated that the JAMM domain of CSN5/Jab1 was essential. CSN5/Jab1-elimination enhanced the neddylation of cullins 1 and 4 and altered the expression of many factors including cyclin E and p53. CSN5/Jab1-elimination inhibited progression of the cell cycle at multiple points, seemed to initiate p53-independent senescence and increased the ploidy of cells. Thus, CSN5/Jab1 controls different events of the cell cycle, preventing senescence and endocycle as well as the proper progression of the somatic cell cycle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • COP9 Signalosome Complex
  • Cell Cycle Proteins / metabolism
  • Cell Cycle*
  • Cell Proliferation
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Gene Knockdown Techniques
  • Gene Silencing
  • Genetic Loci / genetics
  • HEK293 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / chemistry
  • Intracellular Signaling Peptides and Proteins / deficiency
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mice
  • Peptide Hydrolases / chemistry
  • Peptide Hydrolases / deficiency
  • Peptide Hydrolases / genetics
  • Peptide Hydrolases / metabolism*
  • Protein Structure, Tertiary
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Cell Cycle Proteins
  • Intracellular Signaling Peptides and Proteins
  • Tumor Suppressor Protein p53
  • Peptide Hydrolases
  • Cops5 protein, mouse
  • COP9 Signalosome Complex