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 language | English (US) |
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Pages (from-to) | 5075-5081 |
Number of pages | 7 |
Journal | FEBS Letters |
Volume | 581 |
Issue number | 26 |
DOIs | |
State | Published - 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