Hypoxia-induced nucleophosmin protects cell death through inhibition of p53

June Li, Xiaoling Zhang, Daniel P. Sejas, Grover C. Bagby, Qishen Pang

    Research output: Contribution to journalArticle

    114 Citations (Scopus)

    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-1α. 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.

    Original languageEnglish (US)
    Pages (from-to)41275-41279
    Number of pages5
    JournalJournal of Biological Chemistry
    Volume279
    Issue number40
    DOIs
    StatePublished - Oct 1 2004

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    Cell death
    Cell Death
    Hypoxia-Inducible Factor 1
    Cells
    Null Lymphocytes
    Neoplasms
    Phosphorylation
    Proteins
    nucleophosmin
    Hypoxia
    Small Interfering RNA
    Cell Survival
    Up-Regulation
    Chemical activation
    Apoptosis

    ASJC Scopus subject areas

    • Biochemistry

    Cite this

    Hypoxia-induced nucleophosmin protects cell death through inhibition of p53. / Li, June; Zhang, Xiaoling; Sejas, Daniel P.; Bagby, Grover C.; Pang, Qishen.

    In: Journal of Biological Chemistry, Vol. 279, No. 40, 01.10.2004, p. 41275-41279.

    Research output: Contribution to journalArticle

    Li, June ; Zhang, Xiaoling ; Sejas, Daniel P. ; Bagby, Grover C. ; Pang, Qishen. / Hypoxia-induced nucleophosmin protects cell death through inhibition of p53. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 40. pp. 41275-41279.
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    AU - Sejas, Daniel P.

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    N2 - 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-1α. 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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