Department of Biochemistry, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.
Mol Cell Biol. 2010 Jan;30(2):524-36. doi: 10.1128/MCB.00938-09. Epub 2009 Nov 16.
The E2F transcription factors have emerged as critical apoptotic effectors. Herein we report that the E2F family member E2F3a can be induced by DNA damage through transcriptional and posttranslational mechanisms. We demonstrate that the posttranslational induction of human E2F3a is dependent on the checkpoint kinases. Moreover, we show that human E2F3a is a substrate for the checkpoint kinases (chk kinases) and that mutation of the chk phosphorylation site eliminates the DNA damage inducibility of the protein. Furthermore, we demonstrate that E2F1 and E2F2 are transcriptionally induced by DNA damage in an E2f3-dependent manner. Finally, using both in vitro and in vivo approaches, we establish that E2f3 is required for DNA damage-induced apoptosis. Thus, our data reveal the novel ability of E2f3 to function as a master regulator of the DNA damage response.
E2F 转录因子已成为关键的凋亡效应因子。在此，我们报告 E2F 家族成员 E2F3a 可通过转录和翻译后机制被 DNA 损伤诱导。我们证明，人 E2F3a 的翻译后诱导依赖于检查点激酶。此外，我们表明人 E2F3a 是检查点激酶 (chk 激酶) 的底物，chk 磷酸化位点的突变消除了蛋白对 DNA 损伤的诱导能力。此外，我们证明 E2F1 和 E2F2 可通过 E2f3 依赖的方式被 DNA 损伤转录诱导。最后，我们通过体外和体内方法，确定 E2f3 是 DNA 损伤诱导凋亡所必需的。因此，我们的数据揭示了 E2f3 作为 DNA 损伤反应的主调控因子的新功能。
