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 › peer-review

30 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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10.1016/j.febslet.2007.09.052

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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",

author = "Colo, {Georgina P.} and Rosato, {Roberto R.} and Steven Grant and Costas, {M{\'o}nica A.}",

note = "Funding Information: This study was supported by Grants from the Argentine National Research Council (CONICET) and Agencia Nacional de Promoci{\'o}n Cient{\'i}fica y Tecnol{\'o}gica to Dr. M{\'o}nica A. Costas and in part by an American Cancer Society institutional Grant (VCU) to Roberto R. Rosato. We thank Jorge A. Almenara and Stefanie Coe for their technical assistance.",

year = "2007",

month = oct,

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doi = "10.1016/j.febslet.2007.09.052",

language = "English (US)",

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pages = "5075--5081",

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T1 - RAC3 down-regulation sensitizes human chronic myeloid leukemia cells to TRAIL-induced apoptosis

AU - Colo, Georgina P.

AU - Rosato, Roberto R.

AU - Grant, Steven

AU - Costas, Mónica A.

N1 - Funding Information: This study was supported by Grants from the Argentine National Research Council (CONICET) and Agencia Nacional de Promoción Científica y Tecnológica to Dr. Mónica A. Costas and in part by an American Cancer Society institutional Grant (VCU) to Roberto R. Rosato. We thank Jorge A. Almenara and Stefanie Coe for their technical assistance.

PY - 2007/10/30

Y1 - 2007/10/30

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Leukemia

KW - NF-κB

KW - Nuclear receptors coactivator

KW - RAC3

KW - TRAIL

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DO - 10.1016/j.febslet.2007.09.052

M3 - Article

C2 - 17927986

AN - SCOPUS:35348905116

VL - 581

SP - 5075

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JO - FEBS Letters

JF - FEBS Letters

SN - 0014-5793

IS - 26

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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