RAC3 down-regulation sensitizes human chronic myeloid leukemia cells to TRAIL-induced apoptosis |
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Authors: | Colo Georgina P Rosato Roberto R Grant Steven Costas Mónica A |
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Affiliation: | Laboratorio de Biología Molecular y Apoptosis, Instituto de Investigaciones Médicas Alfredo Lanari (IDIM-CONICET), Universidad de Buenos Aires, Combatiente de Malvinas 3150, C1427ARO Buenos Aires, Argentina. |
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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. |
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Keywords: | RAC3, receptor associated coactivator-3 TRAIL, tumor necrosis factor (TNF)- related apoptosis-inducing ligand FLIP, FLICE inhibitory protein AIF, apoptosis-inducing factor |
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