title: Phosphorylation by DNAPK inhibits the DNA-binding function of p53/T antigen complex in vitro.
abstract: Interaction of p53 with Mdm2 is hindered if either protein is phosphorylated by DNA-dependent protein kinase (DNAPK), which may account for the activation of p53 in response to double-stranded DNA breaks. This finding raises the question of whether phosphorylation of p53 by DNAPK may have a general effect on its interaction with other proteins. Here we report that unlike the p53/Mdm2 complex, p53/T antigen complex remains intact following phosphorylation by DNAPK, indicating that the effect of phosphorylation upon p53 interaction is dependent on the protein partner. We have previously shown that a mouse p53/T antigen complex can bind DNA in vitro. This complex, however, was significantly reduced in its ability to bind DNA following treatment with DNAPK. This indicates that although phosphorylation did not disrupt the p53/T antigen complex, it did result in a conformational change leading to an alteration of p53' s ability to bind DNA as a protein complex.
authors.affiliation: Department of Biochemistry, University of California, Riverside 92521, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: Sheppard
authors.forename: X
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism*; D002472:Cell Transformation, Viral; D004247:DNA / Q000378:metabolism*; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D051379:Mice; D016513:Mice, SCID; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D013329:Structure-Activity Relationship; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000952:Antigens, Polyomavirus Transforming; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D016159:Tumor Suppressor Protein p53; D004247:DNA; D051747:DNA-Activated Protein Kinase; D017346:Protein Serine-Threonine Kinases