Phosphorylation on Thr-55 by TAF1 mediates degradation of p53: a role for TAF1 in cell G1 progression.
The largest subunit of TFIID, TAF1, possesses an intrinsic protein kinase activity and is important for cell G1 progression and apoptosis. Since p53 functions by inducing cell G1 arrest and apoptosis, we investigated the link between TAF1 and p53. We found that TAF1 induces G1 progression in a p53-dependent manner. TAF1 interacts with and phosphorylates p53 at Thr-55 in vivo. Substitution of Thr-55 with an alanine residue (T55A) stabilizes p53 and impairs the ability of TAF1 to induce G1 progression. Furthermore, both RNAi-mediated TAF1 ablation and apigenin-mediated inhibition of the kinase activity of TAF1 markedly reduced Thr-55 phosphorylation. Thus, phosphorylation and the resultant degradation of p53 provide a mechanism for regulation of the cell cycle by TAF1. Significantly, the Thr-55 phosphorylation was reduced following DNA damage, suggesting that this phosphorylation contributes to the stabilization of p53 in response to DNA damage.
Li
Heng-Hong
HH
Department of Biochemistry, University of California, Riverside, CA 92521, USA.
Li
Andrew G
AG
Sheppard
Hilary M
HM
Liu
Xuan
X
D000409:Alanine / Q000378:metabolism; D019943:Amino Acid Substitution; D000970:Antineoplastic Agents / Q000494:pharmacology; D047310:Apigenin; D001859:Bone Neoplasms / Q000235:genetics / Q000473:pathology; D002453:Cell Cycle / Q000502:physiology*; D045744:Cell Line, Tumor; D004249:DNA Damage; D004355:Drug Stability; D005419:Flavonoids / Q000494:pharmacology; D016193:G1 Phase; D051548:Histone Acetyltransferases; D006801:Humans; D009687:Nuclear Proteins; D010766:Phosphorylation; D011494:Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D034741:RNA, Small Interfering / Q000378:metabolism; D035381:TATA-Binding Protein Associated Factors / Q000378:metabolism*; D013912:Threonine / Q000378:metabolism*; D035362:Transcription Factor TFIID / Q000378:metabolism*; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000970:Antineoplastic Agents; D005419:Flavonoids; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D035381:TATA-Binding Protein Associated Factors; D035362:Transcription Factor TFIID; D016159:Tumor Suppressor Protein p53; D013912:Threonine; D047310:Apigenin; D051548:Histone Acetyltransferases; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D011494:Protein Kinases; C069001:TATA-binding protein associated factor 250 kDa; D000409:Alanine