Regulation of the specific DNA binding function of p53

T. R. Hupp, D. W. Meek, C. A. Midgley, D. P. Lane

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    834 Citations (Scopus)

    Abstract

    The DNA binding activity of p53 is required for its tumor suppressor function; we show here that this activity is cryptic but can be activated by cellular factors acting on a C-terminal regulatory domain of p53. A gel mobility shift assay demonstrated that recombinant wild-type human p53 binds DNA sequence specifically only weakly, but a monoclonal antibody binding near the C terminus activated the cryptic DNA binding activity stoichiometrically. p53 DNA binding could be activated by a C-terminal deletion of p53, mild proteolysis of full-length p53, E. coli dnaK (which disrupts protein-protein complexes), or casein kinase II (and coincident phosphorylation of a C-terminal site on p53). Activation of p53 DNA binding may be critical in regulation of its ability to arrest cell growth and thus its tumor suppressor function.
    Original languageEnglish
    Pages (from-to)875-886
    Number of pages12
    JournalCell
    Volume71
    Issue number5
    DOIs
    Publication statusPublished - 27 Nov 1992

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    Hupp, T. R., Meek, D. W., Midgley, C. A., & Lane, D. P. (1992). Regulation of the specific DNA binding function of p53. Cell, 71(5), 875-886. https://doi.org/10.1016/0092-8674(92)90562-Q