Activated H-Ras regulates hematopoietic cell survival by modulating Survivin

Seiji Fukuda, Louis M. Pelus

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Survivin expression and Ras activation are regulated by hematopoietic growth factors. We investigated whether activated Ras could circumvent growth factor-regulated Survivin expression and if a Ras/Survivin axis mediates growth factor independent survival and proliferation in hematopoietic cells. Survivin expression is up-regulated by IL-3 in Ba/F3 and CD34 + cells and inhibited by the Ras inhibitor, farnesylthiosalicylic acid. Over-expression of constitutively activated H-Ras (CA-Ras) in Ba/F3 cells blocked down-modulation of Survivin expression, G 0/G 1 arrest, and apoptosis induced by IL-3 withdrawal, while dominant-negative (DN) H-Ras down-regulated Survivin. Survivin disruption by DN T34A Survivin blocked CA-Ras-induced IL-3-independent cell survival and proliferation; however, it did not affect CA-Ras-mediated enhancement of S-phase, indicating that the anti-apoptotic activity of CA-Ras is Survivin dependent while its S-phase enhancing effect is not. These results indicate that CA-Ras modulates Survivin expression independent of hematopoietic growth factors and that a CA-Ras/Survivin axis regulates survival and proliferation of transformed hematopoietic cells.

Original languageEnglish (US)
Pages (from-to)636-644
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume323
Issue number2
DOIs
StatePublished - Oct 15 2004

Keywords

  • Apoptosis
  • Cell cycle
  • Leukemia
  • Ras
  • Survivin

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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