Cell cycle promoting activity of JunB through cyclin A activation

J Biol Chem. 2002 Sep 27;277(39):35961-8. doi: 10.1074/jbc.M202847200. Epub 2002 Jul 16.

Abstract

JunB, a major component of the AP-1 transcription factor, is known to act antagonistically to c-Jun in transcriptional regulation and is proposed to be a negative regulator of cell proliferation. Employing fibroblasts derived from E9.5 junB(-/-) mouse embryos we provide evidence for a novel cell cycle promoting role of JunB. Despite a normal proliferation rate, primary and immortalized junB(-/-) fibroblasts exhibited an altered cell cycle profile, which was characterized by an increase in the population of S-phase cells, while that of cells in G(2)/M-phase was diminished. This delay in G(2)/M-transition is caused by impaired cyclin A-CDK2 and cyclin B-CDC2 kinase activities and counteracts the accelerated S-phase entry. Cells lacking JunB show severely delayed kinetics of cyclin A mRNA expression due to the loss of proper transcriptional activation mediated via binding of JunB to the CRE element in the cyclin A promoter. Upon reintroduction of an inducible JunB-ER(TM) expression vector the cell cycle distribution and the cell cycle-associated cyclin A-CDK2 kinase activity could be restored. Thus, cyclin A is a direct transcriptional target of JunB driving cell proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Blotting, Western
  • Cell Cycle
  • Cell Division
  • Cyclin A / metabolism*
  • Fibroblasts / metabolism
  • Flow Cytometry
  • G2 Phase
  • Genes, Reporter
  • Genetic Vectors
  • Mice
  • Mitosis
  • Models, Biological
  • Models, Genetic
  • Phosphorylation
  • Precipitin Tests
  • Promoter Regions, Genetic
  • Protein Kinases / metabolism
  • Proto-Oncogene Proteins c-jun / physiology*
  • RNA, Messenger / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • S Phase
  • Signal Transduction
  • Time Factors
  • Transcription, Genetic

Substances

  • Cyclin A
  • Proto-Oncogene Proteins c-jun
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Protein Kinases
  • histone H1 kinase