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    Exp Cell Res. 2012 Jan 15;318(2):136-43. Epub 2011 Sep 9.

    Long isoform of ErbB3 binding protein, p48, mediates protein kinase B/Akt-dependent HDM2 stabilization and nuclear localization.

    Kim CK, Lee SB, Nguyen TL, Lee KH, Um SH, Kim J, Ahn JY.

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    Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, 440-746, Republic of Korea.

    Abstract

    p48 is a long isoform of the ErbB3 binding protein that has oncogenic functions including promotion of carcinogenesis and induction of malignant transformation through negative regulation of tumor suppressor p53. Here, we show that high level of p48 protein expression leads to enhance HDM2 phosphorylation by Akt and inhibits the self-ubiquitination of HDM2 by up-regulation of Akt activity, thereby promoting its protein stability. Moreover, p48 expression leads to accumulated nuclear localization of HDM2, whereas p48 depletion disturbs its nuclear localization. Hence, higher expression of p48 in cancer cells reduces p53 levels through modulation of HDM2 nuclear localization and protein stability via regulation of its Akt-mediated phosphorylation.

    Copyright © 2011 Elsevier Inc. All rights reserved.

    PMID:
    21930127
    [PubMed - indexed for MEDLINE]

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