RAC3 down-regulation sensitizes human chronic myeloid leukemia cells to TRAIL-induced apoptosis

Georgina P. Colo, Roberto R. Rosato, Steven Grant, Mónica A. Costas

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

The nuclear receptor coactivator RAC3 plays important roles in many biological processes and tumorigenesis. We found that RAC3 is over-expressed in human chronic myeloid leukemia cells K562, which are normally resistant to TRAIL-induced apoptosis. RAC3 down-regulation by siRNA rendered these cells sensitive to TRAIL-induced cell death. In addition to the up-regulation of TRAIL receptors, the process involves Bid, caspases and PARP activation, loss of mitochondrial membrane potential, and release of AIF, cytochrome c and Smac/DIABLO to the cytoplasm. We conclude that RAC3 is required for TRAIL resistance and that this anti-apoptotic function is independent of its role in hormone receptor signaling.

Original languageEnglish (US)
Pages (from-to)5075-5081
Number of pages7
JournalFEBS Letters
Volume581
Issue number26
DOIs
StatePublished - Oct 30 2007

Keywords

  • Apoptosis
  • Leukemia
  • NF-κB
  • Nuclear receptors coactivator
  • RAC3
  • TRAIL

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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