Borger Darrell R, DeCaprio James A
Dana-Farber Cancer Institute, Department of Medical Oncology, Harvard Medical School, Mayer Building 457, 44 Binney Street, Boston, Massachusetts 02115, USA.
J Virol. 2006 May;80(9):4292-303. doi: 10.1128/JVI.80.9.4292-4303.2006.
The primary transforming functions of simian virus 40 large T antigen (SV40 LT) are conferred primarily through the binding and inactivation of p53 and the retinoblastoma family members. Normal p53 function requires an association with the CREB binding protein (CBP)/p300 coactivators, and a ternary complex containing SV40 LT, p53, and CBP/p300 has been identified previously. In this report, we have evaluated a secondary function of p53 bound to the SV40 LT complex in mediating the binding of human CBP/p300. We demonstrate that p53 associated with SV40 LT was posttranslationally modified in a manner consistent with the binding of CBP/p300. Furthermore, expression of SV40 LT induced the proportion of p53 phosphorylated on S15. An essential function for p53 in bridging the interaction between SV40 LT and CBP/p300 was identified through the reconstitution of the SV40 LT-CBP/p300 complex upon p53 reexpression in p53-null cells. In addition, the SV40 LT-CBP/p300 complex was disrupted through RNA interference-mediated depletion of endogenous p53. We also demonstrate that SV40 LT was acetylated in a p300- and p53-dependent manner, at least in part through the CH3 domain of p300. Therefore, the binding of p53 serves to modify SV40 LT by targeting CBP and p300 binding to direct the acetylation of SV40 LT.
猿猴病毒40大T抗原（SV40 LT）的主要转化功能主要是通过与p53及视网膜母细胞瘤家族成员的结合和失活来实现的。正常的p53功能需要与CREB结合蛋白（CBP）/p300共激活因子结合，并且先前已经鉴定出一种包含SV40 LT、p53和CBP/p300的三元复合物。在本报告中，我们评估了与SV40 LT复合物结合的p53在介导人CBP/p300结合中的次要功能。我们证明，与SV40 LT相关的p53在翻译后以与CBP/p300结合一致的方式被修饰。此外，SV40 LT的表达诱导了S15位点磷酸化的p53比例。通过在p53缺失细胞中重新表达p53来重建SV40 LT-CBP/p300复合物，确定了p53在桥接SV40 LT与CBP/p300之间相互作用中的重要功能。此外，通过RNA干扰介导的内源性p53缺失破坏了SV40 LT-CBP/p300复合物。我们还证明，SV40 LT至少部分通过p300的CH3结构域以p300和p53依赖的方式被乙酰化。因此，p53的结合通过靶向CBP和p300的结合来修饰SV40 LT，以指导SV40 LT的乙酰化。
