title: Phosphorylation of p53 by TAF1 inactivates p53-dependent transcription in the DNA damage response.
abstract: While p53 activation has long been studied, the mechanisms by which its targets genes are restored to their preactivation state are less clear. We report here that TAF1 phosphorylates p53 at Thr55, leading to dissociation of p53 from the p21 promoter and inactivation of transcription late in the DNA damage response. We further show that cellular ATP level might act as a molecular switch for Thr55 phosphorylation on the p21 promoter, indicating that TAF1 is a cellular ATP sensor. Upon DNA damage, cells undergo PARP-1-dependent ATP depletion, which is correlated with reduced TAF1 kinase activity and Thr55 phosphorylation, resulting in p21 activation. As cellular ATP levels recover, TAF1 is able to phosphorylate p53 on Thr55, which leads to dissociation of p53 from the p21 promoter. ChIP-sequencing analysis reveals p53 dissociates from promoters genome wide as cells recover from DNA damage, suggesting the general nature of this mechanism.
authors.affiliation: Department of Biochemistry, University of California, Riverside, Riverside, CA 92521, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Biochemistry, University of California, Riverside, Riverside, CA 92521, USA.
authors.forename: Joy C
authors.initials: JC
authors.lastname: Lin
authors.affiliation: Department of Biochemistry, University of California, Riverside, Riverside, CA 92521, USA.
authors.forename: Landon G
authors.initials: LG
authors.lastname: Piluso
authors.affiliation: Department of Biochemistry, University of California, Riverside, Riverside, CA 92521, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Dhahbi
authors.affiliation: Department of Biochemistry, University of California, Riverside, Riverside, CA 92521, USA.
authors.forename: Selene
authors.initials: S
authors.lastname: Bobadilla
authors.affiliation: Department of Biochemistry, University of California, Riverside, Riverside, CA 92521, USA.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Spindler
authors.affiliation: Department of Biochemistry, University of California, Riverside, Riverside, CA 92521, USA. Electronic address: xuan.liu@ucr.edu.
authors.forename: Xuan
authors.initials: X
authors.lastname: Liu
mesh_terms: D000255:Adenosine Triphosphate / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D055106:Genome-Wide Association Study; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation / Q000235:genetics; D011401:Promoter Regions, Genetic; D035381:TATA-Binding Protein Associated Factors / Q000235:genetics / Q000378:metabolism*; D035362:Transcription Factor TFIID / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D035381:TATA-Binding Protein Associated Factors; C495901:TP53 protein, human; D035362:Transcription Factor TFIID; D016159:Tumor Suppressor Protein p53; D000255:Adenosine Triphosphate; D051548:Histone Acetyltransferases; C069001:TATA-binding protein associated factor 250 kDa