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首页> 外文期刊>Molecular and Cellular Biology >The Molecular Chaperone Activity of Simian Virus 40 Large T Antigen Is Required To Disrupt Rb-E2F Family Complexes by an ATP-Dependent Mechanism
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The Molecular Chaperone Activity of Simian Virus 40 Large T Antigen Is Required To Disrupt Rb-E2F Family Complexes by an ATP-Dependent Mechanism

机译：通过ATP依赖机制破坏猿Rb-E2F家族复合体需要猿猴病毒40大T抗原的分子伴侣活性。

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The simian virus 40 large T antigen (T antigen) inactivates tumor suppressor proteins and therefore has been used in numerous studies to probe the mechanisms that control cellular growth and to generate immortalized cell lines. Binding of T antigen to the Rb family of growth-regulatory proteins is necessary but not sufficient to cause transformation. The molecular mechanism underlying T-antigen inactivation of Rb function is poorly understood. In this study we show that T antigen associates with pRb and p130-E2F complexes in a stable manner. T antigen dissociates from a p130–E2F-4–DP-1 complex, coincident with the release of p130 from E2F-4–DP-1. The dissociation of this complex requires Hsc70, ATP, and a functional T-antigen J domain. We also report that the “released” E2F–DP-1 complex is competent to bind DNA containing an E2F consensus binding site. We propose that T antigen disrupts Rb-E2F family complexes through the action of its J domain and Hsc70. These findings indicate how Hsc70 supports T-antigen action and help to explain the cisrequirement for a J domain and Rb binding motif in T-antigen-induced transformation. Furthermore, this is the first demonstration linking Hsc70 ATP hydrolysis to the release of E2F bound by Rb family members.
机译：猿猴病毒40大T抗原（T抗原）使肿瘤抑制蛋白失活，因此已在众多研究中用于探测控制细胞生长并产生永生化细胞系的机制。 T抗原与生长调节蛋白的Rb家族结合是必要的，但不足以引起转化。对Rb功能的T抗原失活的分子机制了解甚少。在这项研究中，我们表明T抗原以稳定的方式与pRb和p130-E2F复合体缔合。 T抗原从p130–E2F-4–DP-1复合物中解离，这与p130从E2F-4–DP-1中释放有关。该复合物的解离需要Hsc70，ATP和功能性T抗原J结构域。我们还报告说，“释放的” E2F-DP-1复合物能够结合含有E2F共有结合位点的DNA。我们建议，T抗原通过其J结构域和Hsc70的作用破坏Rb-E2F家族复合物。这些发现表明Hsc70如何支持T抗原的作用，并有助于解释在T抗原诱导的转化中J结构域和Rb结合基序的 cis 需求。此外，这是将Hsc70 ATP水解与Rb家族成员结合的E2F释放联系起来的第一个证明。

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