Regulation of the specific DNA binding function of p53

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

    Research output: Contribution to journalArticle

    822 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

    Fingerprint

    DNA
    Tumors
    Proteolysis
    Casein Kinase II
    Phosphorylation
    DNA sequences
    Cell growth
    Electrophoretic Mobility Shift Assay
    Protein Kinases
    Escherichia coli
    Assays
    Neoplasms
    Proteins
    Gels
    Chemical activation
    Monoclonal Antibodies
    Growth

    Cite this

    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
    Hupp, T. R. ; Meek, D. W. ; Midgley, C. A. ; Lane, D. P. / Regulation of the specific DNA binding function of p53. In: Cell. 1992 ; Vol. 71, No. 5. pp. 875-886.
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    Hupp, TR, Meek, DW, Midgley, CA & Lane, DP 1992, 'Regulation of the specific DNA binding function of p53', Cell, vol. 71, no. 5, pp. 875-886. https://doi.org/10.1016/0092-8674(92)90562-Q

    Regulation of the specific DNA binding function of p53. / Hupp, T. R.; Meek, D. W.; Midgley, C. A.; Lane, D. P.

    In: Cell, Vol. 71, No. 5, 27.11.1992, p. 875-886.

    Research output: Contribution to journalArticle

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    AB - 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.

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    Hupp TR, Meek DW, Midgley CA, Lane DP. Regulation of the specific DNA binding function of p53. Cell. 1992 Nov 27;71(5):875-886. https://doi.org/10.1016/0092-8674(92)90562-Q