期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 420, 期 4, 页码 913-917出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2012.03.101
关键词
Hypoxia; HIF-1 alpha; ARC; Colon cancer cells; Apoptosis
Apoptosis repressor with caspase recruitment domain (ARC), an anti-apoptotic protein, plays an important role in the regulation of apoptosis by blocking both the extrinsic and intrinsic death pathways. However, its regulatory mechanism remains largely undefined. Here, we reported that hypoxia up-regulated the expression of ARC in p53 deficient human colon cancer cells. Moreover, ARC is a direct target of the hypoxia-inducible factor 1 (HIF-1), a key transcriptional factor for the cellular response to hypoxia. Silencing the expression of HIF-1 alpha in SW480 colon cancer cells by RNA interference abolished hypoxia induced ARC expression. Using luciferase reporter and ChIP assay, we showed that HIF-1 alpha directly bound to hypoxia-responsive element located at -419 to -414 of ARC gene, which is essential for HIF-1-induced expression. As a result of the increased ARC expression, TRAIL-induced apoptosis was reduced by hypoxia. These discoveries would shed novel insights on the mechanisms for ARC expression regulation and hypoxia induced inactivation of the intrinsic death pathway. (C) 2012 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据