下调和上调
细胞生物学
癌症研究
细胞周期
环己酰亚胺
细胞周期检查点
细胞凋亡
细胞周期蛋白依赖激酶
阿霉素
CDK抑制剂
化学
生物
分子生物学
蛋白质生物合成
生物化学
化疗
基因
遗传学
作者
David W. Clark,Aparna Mitra,Rebecca A. Fillmore,Wen Guo Jiang,Rajeev S. Samant,Øystein Fodstad,Lalita A. Shevde
出处
期刊:Current Cancer Drug Targets
[Bentham Science]
日期:2008-08-01
卷期号:8 (5): 421-430
被引量:66
标识
DOI:10.2174/156800908785133196
摘要
Nuclear protein 1 (NUPR1/com1/p8) has been shown to interact with transcriptional regulators such as p300, PTIP, estrogen receptor-β, and SMAD. NUPR1 also has been implicated in the regulation of cell cycle and apoptosis. An increase in NUPR1 expression has been seen with serum starvation and in response to compounds such as cycloheximide, ceramide, and staurosporine. There are several overtly conflicting reports about the exact role of NUPR1 in tumor biology. This work investigates the nature of the relationship between NUPR1 and the cdk-inhibitor p21 (Waf1/Cip1) expression. We show that the expression of resident and doxorubicin-induced p21 paralleled that of endogenous NUPR1 levels. NUPR1 formed a complex with p53 and p300 and bound the p21 promoter and transcriptionally upregulated p21 expression. Moreover, NUPR1 allowed cells to progress through cell cycle in presence of doxorubicin. Since NUPR1 upregulated p21, concomitant with phosphorylation of Rb and upregulation of the anti-apoptotic protein, Bcl-xL we propose that NUPR1 expression imparts a cell growth and survival advantage. Importantly, we also report that NUPR1 conferred resistance to two chemotherapeutic drugs, Taxol and doxorubicin. Keywords: NUPR1, com1, p8, p53, p21, cell cycle, doxorubicin, taxol
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