p53 targets Simian virus 40 large T antigen for acetylation by CBP
p53 targets Simian virus 40 large T antigen for acetylation by CBP
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DOI：
10.1128/jvi.78.15.8245-8253.2004
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发表时间：
2004-08-01
影响因子：
5.4
通讯作者：
DeCaprio, JA
中科院分区：
文献类型：
--
作者：
Poulin, DL;Kung, AL;DeCaprio, JA
猴病毒40（SV 40）大T抗原（T Ag）与肿瘤抑制因子p53和转录辅激活因子CBP和p300相互作用。这些细胞蛋白在三元复合物中的结合已经涉及T Ag介导的转化。CBP/p300调节p53功能的能力是p53调节细胞增殖和肿瘤发生的基础。在这项研究中，我们提供了进一步的证据表明，CBP的活性可能是通过其与p53的协同作用介导的。我们证明，SV 40 T Ag在体内以p53依赖的方式乙酰化，并且T Ag乙酰化主要由CBP介导。T Ag的乙酰化依赖于其与p53的相互作用以及p53与CBP的相互作用。我们已经绘制了乙酰化的T抗原的C-末端赖氨酸残基697的网站。该乙酰化位点在人多瘤病毒JC和BK的T抗原之间是保守的，其也已知与p53相互作用。我们表明，JC和BK T抗原也乙酰化在相应的网站在体内。虽然已知其他蛋白质被CBP/p300乙酰化，但已知没有蛋白质依赖于p53进行乙酰化。T抗原乙酰化可能为T抗原与细胞因子的结合提供了一种调节机制，或者在T抗原功能的另一个方面发挥作用。
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.