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- Title
RAC3 down-regulation sensitizes human chronic myeloid leukemia cells to TRAIL-induced apoptosis
- Authors
Colo, Georgina P.; Rosato, Roberto R.; Grant, Steven; Costas, Mónica A.
- Abstract
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.
- Subjects
NUCLEAR receptors (Biochemistry); CARCINOGENESIS; HORMONE receptors; CELLS
- Publication
FEBS Letters, 2007, Vol 581, Issue 26, p5075
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/j.febslet.2007.09.052