Groups of p53 target genes involved in specific p53 downstream effects cluster into different classes of DNA binding sites

Hua Qian, Ting Wang, Louie Naumovski, Charles D. Lopez, Rainer K. Brachmann

    Research output: Contribution to journalArticlepeer-review

    110 Scopus citations

    Abstract

    The tumor suppressor protein p53, once activated, can cause either cell cycle arrest or apoptosis through transactivation of target genes with p53 DNA binding sites (DBS). To investigate the role of p53 DBS in the regulation of this profound, yet poorly understood decision of life versus death, we systematically studied all known and potential p53 DBS. We analysed the DBS separated from surrounding promoter regions in yeast and mammalian assays with and without DNA damage. p53 efficiently utilized the DBS of MDM2 and of genes connected to cell cycle arrest, DNA repair and the death receptor pathway of apoptosis. However, p53 was unable to utilize two-thirds of the isolated DBS, a subset that included almost all DBS of apoptosis-related genes. Neither ASPP2, a p53-interacting protein reported to specifically stimulate p53 transcriptional activity on apoptosis-related promoters, nor DNA damage resulted in p53 utilization of isolated DBS of apoptosis-related genes. Thus, a major regulation of p53 activity occurs at the level of p53 DBS themselves by posing additional requirements for the successful utilization of apoptosis-related DBS.

    Original languageEnglish (US)
    Pages (from-to)7901-7911
    Number of pages11
    JournalOncogene
    Volume21
    Issue number51
    DOIs
    StatePublished - Nov 7 2002

    Keywords

    • Apoptosis
    • Cell cycle
    • DNA binding site
    • DNA repair
    • P53

    ASJC Scopus subject areas

    • Molecular Biology
    • Genetics
    • Cancer Research

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