Reduced Ran expression in Ran(+/-) fibroblasts increases cytokine-stimulated nuclear abundance of the AP-1 subunits c-Fos and c-Jun

FEBS Lett. 2010 Nov 19;584(22):4623-6. doi: 10.1016/j.febslet.2010.10.030. Epub 2010 Oct 21.

Abstract

Ran (Ras-related nuclear protein), a Ras family GTPase, is involved in multiple cellular functions, including the regulation of DNA replication, cell cycle progression, nuclear structure formation, RNA processing-exportation, and nuclear protein importation. Ran(+/-) embryonic stem (ES) cells were produced in an attempt to generate Ran null mutant mice. Even after an extremely large number of blastocyst injections, no Ran(+/-) chimeric mice could be generated. Ran(+/-) ES cell-derived fibroblasts showed reduced Ran protein expression, and manifested augmented nuclear abundance of AP-1 factors (c-Jun and c-Fos) upon cytokine stimulation. Our experiments demonstrated that intracellular Ran protein levels controlled the nuclear presence of certain transcription factors, such as c-Fos and c-Jun.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic-Leucine Zipper Transcription Factors / metabolism*
  • Cell Nucleus / drug effects*
  • Cell Nucleus / metabolism
  • Cytokines / pharmacology*
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Gene Expression Regulation / drug effects*
  • Mice
  • Protein Subunits / metabolism*
  • Proto-Oncogene Proteins c-fos / metabolism
  • Proto-Oncogene Proteins c-jun / metabolism
  • Transcription Factor AP-1 / metabolism
  • ran GTP-Binding Protein / metabolism*

Substances

  • Basic-Leucine Zipper Transcription Factors
  • Cytokines
  • Protein Subunits
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • Transcription Factor AP-1
  • ran GTP-Binding Protein