p53 targets simian virus 40 large T antigen for acetylation by CBP.
Simian virus 40 (SV40) large T antigen (T Ag) interacts with the tumor suppressor p53 and the transcriptional coactivators CBP and p300. Binding of these cellular proteins in a ternary complex has been implicated in T Ag-mediated transformation. It has been suggested that the ability of CBP/p300 to modulate p53 function underlies p53's regulation of cell proliferation and tumorigenesis. In this study, we provide further evidence that CBP activity may be mediated through its synergistic action with p53. We demonstrate that SV40 T Ag is acetylated in vivo in a p53-dependent manner and T Ag acetylation is largely mediated by CBP. The acetylation of T Ag is dependent on its interaction with p53 and on p53's interaction with CBP. We have mapped the site of acetylation on T Ag to the C-terminal lysine residue 697. This acetylation site is conserved between the T antigens of the human polyomaviruses JC and BK, which are also known to interact with p53. We show that both JC and BK T antigens are also acetylated at corresponding sites in vivo. While other proteins are known to be acetylated by CBP/p300, none are known to depend on p53 for acetylation. T Ag acetylation may provide a regulatory mechanism for T Ag binding to a cellular factor or play a role in another aspect of T Ag function.
Poulin
Danielle L
DL
Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.
Kung
Andrew L
AL
DeCaprio
James A
JA
D000107:Acetylation; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism*; D019556:COS Cells; D050882:CREB-Binding Protein; D002522:Chlorocebus aethiops; D006801:Humans; D008239:Lysine / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D015534:Trans-Activators / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000952:Antigens, Polyomavirus Transforming; D009687:Nuclear Proteins; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; C494364:Crebbp protein, mouse; D008239:Lysine