Sp1 and p73 activate PUMA following serum starvation

被引：68

作者：

Ming, Lihua

Sakaida, Tsukasa

Yue, Wen

Jha, Anupma

Zhang, Lin

Yu, Jian ^{[1
]}

机构：

[1] Univ Pittsburgh, Inst Canc, Hillman Canc Ctr Res Pavil, Dept Pathol,Sch Med, Pittsburgh, PA 15213 USA

来源：

CARCINOGENESIS | 2008年 / 29卷 / 10期

关键词：

D O I：

10.1093/carcin/bgn150

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

p53-upregulated modulator of apoptosis (PUMA) plays an essential role in p53-dependent apoptosis following DNA damage. PUMA also mediates apoptosis independent of p53. In this study, we investigated the role and mechanism of PUMA induction in response to serum starvation in p53-deficient cancer cells. Following serum starvation, the binding of Sp1 to the PUMA promoter significantly increased, whereas inhibition of Sp1 completely abrogated PUMA induction. p73 was found to be upregulated by serum starvation and mediate PUMA induction through the p53-binding sites in the PUMA promoter. Sp1 and p73 beta appeared to cooperatively activate PUMA transcription, which is inhibited by the phosphoinsitide 3-kinase (PI3K)-protein kinase B (AKT) pathway. Furthermore, knockdown of PUMA suppressed serum starvation-induced apoptosis in leukemia cells. Our results suggest that transcription factors Sp1 and p73 mediate p53-independent induction of PUMA following serum starvation to trigger apoptosis in human cancer cells.

引用

收藏

页码：1878 / 1884

页数：7

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