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Comparative Study
. 2004 Oct 1;279(40):41275-9.
doi: 10.1074/jbc.C400297200. Epub 2004 Aug 13.

Hypoxia-induced nucleophosmin protects cell death through inhibition of p53

June Li  1 , Xiaoling Zhang, Daniel P Sejas, Grover C Bagby, Qishen Pang
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Free article
Comparative Study

Hypoxia-induced nucleophosmin protects cell death through inhibition of p53

"VSports注册入口" June Li et al. J Biol Chem. .
Free article

"VSports app下载" Abstract

Nucleophosmin (NPM) is a multifunctional protein that is overexpressed in actively proliferating cells and cancer cells. Here we report that this proliferation-promoting protein is strongly induced in response to hypoxia in human normal and cancer cells. Up-regulation of NPM is hypoxia-inducible factor-1 (HIF-1)-dependent. The NPM promoter encodes a functional HIF-1-responsive element that can be activated by hypoxia or forced expression of HIF-1alpha VSports手机版. Suppression of NPM expression by small interfering RNA targeting NPM increases hypoxia-induced apoptosis, whereas overexpression of NPM protects against hypoxic cell death of wild-type but not p53-null cells. Moreover, NPM inhibits hypoxia-induced p53 phosphorylation at Ser-15 and interacts with p53 in hypoxic cells. Thus, this study not only demonstrates hypoxia regulation of a proliferation-promoting protein but also suggests that hypoxia-driven cancer progression may require increased expression of NPM to suppress p53 activation and maintain cell survival. .

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