Induction of colonic epithelial cell apoptosis by p47‐dependent oxidants

FEBS Letters

Souza, Rhonda F¹  Gu, Ying¹  Terada, Lance S¹  Xu, You Cheng¹  Wu, Ru Feng¹ 

[1] Department of Internal Medicine, University of Texas Southwestern and the Dallas VAMC, Mail Code 151, 4500 S. Lancaster Rd., Dallas, TX 75216, USA

关键词: Oxidants;    Superoxide;    NADPH oxidase;    Colon cancer;    c-Abl;    Abl interactor-1;   

DOI  :  10.1016/S0014-5793(03)00262-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Exogenous oxidants appear capable of initiating both proliferative and death signals, but the role of endogenous oxidants in either tumorigenesis or tumor suppression is unclear. We found that expression of the NAD(P)H oxidase adapter p47 ^phox was suppressed in human colon carcinoma specimens relative to adjacent normal colon. Overexpression of p47 ^phox increased apoptosis in colon cancer cell lines independent of p53 and mismatch-repair competency. p47 ^phox was found to interact with the c-Abl adapter Abl interactor-1 (ABI-1), and p47 ^phox coprecipitated with both ABI-1 and c-Abl. Ectopic expression of p47 ^phox in colon cancer cells increased oxidant production with phosphorylation and activation of nuclear c-Abl and consequent apoptosis. Colonic epithelial p47 ^phox may be specifically targeted to a c-Abl-containing complex that serves a physiologic tumor suppressing function.

【 授权许可】

Unknown