p53 isoform Delta 113p53 is a p53 target gene that antagonizes p53 apoptotic activity via BclxL activation in zebrafish

Jun Chen, Sok Meng Ng, Changqing Chang, Zhenhai Zhang, Jean-Christophe Bourdon, David P. Lane, Jinrong Peng

    Research output: Contribution to journalArticle

    112 Citations (Scopus)

    Abstract

    p53 is a well-known tumor suppressor and is also involved in processes of organismal aging and developmental control. A recent exciting development in the p53 field is the discovery of various p53 isoforms. One p53 isoform is human Delta 133p53 and its zebrafish counterpart Delta 113p53. These N-terminal-truncated p53 isoforms are initiated from an alternative p53 promoter, but their expression regulation and physiological significance at the organismal level are not well understood. We show here that zebrafish Delta 113p53 is directly transactivated by full-length p53 in response to developmental and DNA-damaging signals. More importantly, we show that Delta 113p53 functions to antagonize p53-induced apoptosis via activating bcl2L (closest to human Bcl-x(L)), and knockdown of Delta 113p53 enhances p53-mediated apoptosis under stress conditions. Thus, we demonstrate that the p53 genetic locus contains a new p53 response gene and that Delta 113p53 does not act in a dominant-negative manner toward p53 but differentially modulates p53 target gene expression to antagonize p53 apoptotic activity at the physiological level in zebrafish. Our results establish a novel feedback pathway that modulates the p53 response and suggest that modulation of the p53 pathway by p53 isoforms might have an impact on p53 tumor suppressor activity.

    Original languageEnglish
    Pages (from-to)278-290
    Number of pages13
    JournalGenes & Development
    Volume23
    Issue number3
    DOIs
    Publication statusPublished - 1 Feb 2009

    Keywords

    • p53 isoforms
    • Delta 113p53
    • Bcl2
    • apoptosis
    • zebrafish
    • EXPRESSION
    • TRANSACTIVATION
    • IDENTIFICATION
    • NETWORK
    • PROTEIN
    • ARREST
    • CANCER

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