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RAC3 down‐regulation sensitizes human chronic myeloid leukemia cells to TRAIL‐induced apoptosis
Author(s) -
Colo Georgina P.,
Rosato Roberto R.,
Grant Steven,
Costas Mónica A.
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.09.052
Subject(s) - apoptosis , microbiology and biotechnology , myeloid leukemia , coactivator , caspase , cancer research , programmed cell death , k562 cells , carcinogenesis , receptor , leukemia , chemistry , intrinsic apoptosis , biology , immunology , biochemistry , transcription factor , gene
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.