title: Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain.
abstract: The tumor suppressor p53 exerts antiproliferation effects through its ability to function as a sequence-specific DNA-binding transcription factor. Here, we demonstrate that p53 can be modified by acetylation both in vivo and in vitro. Remarkably, the site of p53 that is acetylated by its coactivator, p300, resides in a C-terminal domain known to be critical for the regulation of p53 DNA binding. Furthermore, the acetylation of p53 can dramatically stimulate its sequence-specific DNA-binding activity, possibly as a result of an acetylation-induced conformational change. These observations clearly indicate a novel pathway for p53 activation and, importantly, provide an example of an acetylation-mediated change in the function of a nonhistone regulatory protein. These results have significant implications regarding the molecular mechanisms of various acetyltransferase-containing transcriptional coactivators whose primary targets have been presumed to be histones.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, New York 10021, USA.
authors.forename: W
authors.initials: W
authors.lastname: Gu
authors.forename: R G
authors.initials: RG
authors.lastname: Roeder
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D019143:Evolution, Molecular; D051548:Histone Acetyltransferases; D006801:Humans; D008956:Models, Chemical; D008969:Molecular Sequence Data; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism*; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
chemical_list: D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D004247:DNA; D051548:Histone Acetyltransferases; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor