Work

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

Year: 2007

Type: article

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.

Source: FEBS Letters

DOI: 10.1016/j.febslet.2007.09.052

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