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

被引：35

作者：

Colo, Georgina P.

Rosato, Roberto R.

Grant, Steven

Costas, Monica A.

机构：

[1] Univ Buenos Aires, CONICET, Inst Invest Med Alfredo Lanari, IDIM,Lab Biol Mol & Apoptosis, Buenos Aires, DF, Argentina

[2] Virginia Commonwealth Univ, Massey Canc Ctr, Dept Med, Richmond, VA 23298 USA

[3] Virginia Commonwealth Univ, Massey Canc Ctr, Dept Biochem, Richmond, VA 23298 USA

来源：

FEBS LETTERS | 2007年 / 581卷 / 26期

关键词：

nuclear receptors coactivator; RAC3; apoptosis; leukemia; TRAIL; NF-kappa B;

D O I：

10.1016/j.febslet.2007.09.052

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：5075 / 5081

页数：7

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