Regulation of the specific DNA binding function of p53.
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.
Hupp
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Cancer Research Campaign Laboratories, Department of Biochemistry, University of Dundee, Scotland.
Meek
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Midgley
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Lane
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DP
D000818:Animals; D000937:Antigen-Antibody Reactions; D001483:Base Sequence; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism*; D047388:Casein Kinases; D002478:Cells, Cultured; D006360:Heat-Shock Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014357:Trypsin / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000276:immunology / Q000378:metabolism*
D002352:Carrier Proteins; D006360:Heat-Shock Proteins; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D011494:Protein Kinases; D047388:Casein Kinases; D014357:Trypsin