Wei Yuanyan, Liu Dan, Ge Yuqing, Zhou Fengbiao, Xu Jiejie, Chen Hong, Gu Jianxin, Jiang Jianhai
Key Laboratory of Glycoconjuates Research & Gene Research Center, Shanghai Medical College of Fudan University, Shanghai, People's Republic of China.
J Biochem. 2008 Oct;144(4):539-46. doi: 10.1093/jb/mvn098. Epub 2008 Aug 7.
Transcription factor E1AF plays critical roles in neuronal development and tumour metastasis and is regulated by a number of signalling cascades, including the mitogen-activated protein kinase pathways. Accumulated evidence indicted that E1AF might contribute to cell survival in response to environment factors. Here, we provided evidence the cell cycle and apoptosis regulator E2F1 induces E1AF expression at the transcriptional level. DNA damage by etoposide causes E2F1-dependent induction of E1AF expression at transcriptional level. Furthermore, disruption of E1AF expression by E1AF RNAi decreased E2F1-induced apoptosis in response to etoposide. Thus, we conclude that activation of E1AF provides a means for E2F1 to induce cell apoptosis in response to DNA damage.
转录因子E1AF在神经元发育和肿瘤转移中发挥关键作用，并受包括丝裂原活化蛋白激酶途径在内的多种信号级联调控。越来越多的证据表明，E1AF可能有助于细胞在环境因素作用下存活。在此，我们提供证据表明细胞周期和凋亡调节因子E2F1在转录水平上诱导E1AF表达。依托泊苷引起的DNA损伤导致E2F1在转录水平上依赖性诱导E1AF表达。此外，通过E1AF RNA干扰破坏E1AF表达可降低E2F1诱导的依托泊苷诱导的细胞凋亡。因此，我们得出结论，E1AF的激活为E2F1诱导细胞对DNA损伤作出凋亡反应提供了一种方式。
