Expression of Rac1b stimulates NF-kappaB-mediated cell survival and G1/S progression

Exp Cell Res. 2005 May 1;305(2):292-9. doi: 10.1016/j.yexcr.2004.12.029.

Abstract

The small GTPase Rac1 can stimulate various signaling pathways following a tightly controlled GDP-GTP exchange. A splicing variant designated Rac1b was found to exist predominantly in the active GTP-bound state but the functional consequences of its expression remain unknown. Here we used mouse fibroblasts as a model to assess the signaling properties of Rac1b. We show that, in contrast to Rac1, expression of wild-type Rac1b is sufficient to stimulate cyclin D1 accumulation and G1/S progression in these cells. Moreover, expression of wild-type Rac1b, but not of wild-type Rac1, dramatically increased cell survival in the presence of only minimal growth stimuli. Both cellular responses were blocked by the NF-kappaB super-repressor IkappaBalpha(A32A36). Active Rac1b induced the phosphorylation and membrane translocation of IkappaBalpha, a prerequisite for the activation of NF-kappaB. These data demonstrate that Rac1b is a highly active Rac1 variant that stimulates cell cycle progression and cell survival in pathways involving NF-kappaB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle / physiology*
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism
  • Cell Survival
  • G1 Phase
  • Humans
  • I-kappa B Proteins / metabolism
  • Mice
  • NF-kappa B / analysis
  • NF-kappa B / metabolism*
  • NIH 3T3 Cells
  • Neuropeptides / genetics
  • Neuropeptides / physiology*
  • Phosphorylation
  • Protein Transport / physiology
  • S Phase
  • Signal Transduction*
  • rac GTP-Binding Proteins / genetics
  • rac GTP-Binding Proteins / physiology*
  • rac1 GTP-Binding Protein

Substances

  • I-kappa B Proteins
  • NF-kappa B
  • Neuropeptides
  • RAC1 protein, human
  • rac GTP-Binding Proteins
  • rac1 GTP-Binding Protein