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

Georgina P. Colo; Roberto R. Rosato; Steven Grant; Mónica A. Costas

doi:10.1016/j.febslet.2007.09.052

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

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

Research output: Contribution to journal › Article

28 Scopus citations

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)
Pages (from-to)	5075-5081
Number of pages	7
Journal	FEBS Letters
Volume	581
Issue number	26
DOIs	https://doi.org/10.1016/j.febslet.2007.09.052
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

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title = "RAC3 down-regulation sensitizes human chronic myeloid leukemia cells to TRAIL-induced apoptosis",

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.",

keywords = "Apoptosis, Leukemia, NF-κB, Nuclear receptors coactivator, RAC3, TRAIL",

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AU - Costas, Mónica A.

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