E2F的细胞周期蛋白A结合位点在调控p53诱导的DNA损伤应答凋亡中的新功能。
Novel function of the cyclin A binding site of E2F in regulating p53-induced apoptosis in response to DNA damage.
作者信息
Hsieh Jung-Kuang, Yap Damian, O'Connor Daniel J, Fogal Valentina, Fallis Lynn, Chan Florence, Zhong Shan, Lu Xin
机构信息
Ludwig Institute for Cancer Research, Imperial College School of Medicine, London W2 1PG, United Kingdom.
出版信息
Mol Cell Biol. 2002 Jan;22(1):78-93. doi: 10.1128/MCB.22.1.78-93.2002.
Abstract
We demonstrate here that the E2F1 induced by DNA damage can bind to and promote the apoptotic function of p53 via the cyclin A binding site of E2F1. This function of E2F1 does not require its DP-1 binding, DNA binding, or transcriptional activity and is independent of mdm2. All the cyclin A binding E2F family members can interact and cooperate with p53 to induce apoptosis. This suggests a novel role for E2F in regulating apoptosis in response to DNA damage. Cyclin A, but not cyclin E, prevents E2F1 from interacting and cooperating with p53 to induce apoptosis. However, in response to DNA damage, cyclin A levels decrease, with a concomitant increase in E2F1-p53 complex formation. These results suggest that the binding of E2F1 to p53 can specifically stimulate the apoptotic function of p53 in response to DNA damage.
摘要
我们在此证明，DNA损伤诱导产生的E2F1可通过E2F1的细胞周期蛋白A结合位点与p53结合并促进其凋亡功能。E2F1的这一功能不需要其与DP-1结合、DNA结合或转录活性，并且不依赖于mdm2。所有结合细胞周期蛋白A的E2F家族成员都能与p53相互作用并协同诱导凋亡。这表明E2F在调节DNA损伤反应中的凋亡过程中具有新的作用。细胞周期蛋白A而非细胞周期蛋白E可阻止E2F1与p53相互作用并协同诱导凋亡。然而，在DNA损伤反应中，细胞周期蛋白A水平降低，同时E2F1-p53复合物形成增加。这些结果表明，E2F1与p53的结合可特异性刺激p53在DNA损伤反应中的凋亡功能。
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