4.5 Article

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

Journal

FEBS LETTERS
Volume 584, Issue 22, Pages 4623-4626

Publisher

WILEY
DOI: 10.1016/j.febslet.2010.10.030

Keywords

Ran; Mouse gene knockout; c-Jun and c-Fos

Funding

  1. Canadian Institutes of Health Research [MOP57697, MOP69089, PPP86159, IMH-79565, MOP97829]
  2. Heart and Stroke Foundation of Quebec
  3. J.-Louis Levesque Foundation
  4. Fonds de la recherche en sante du Quebec (FRSQ) for Transfusional and Hemovigilance Medical Research

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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. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

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