在人宫颈癌HeLa细胞中，活化转录因子5（ATF5）通过上调细胞周期蛋白D3转录来增加顺铂诱导的细胞凋亡。
ATF5 increases cisplatin-induced apoptosis through up-regulation of cyclin D3 transcription in HeLa cells.
作者信息
Wei Yuanyan, Jiang Jianhai, Sun Maoyun, Chen Xiaoning, Wang Hanzhou, Gu Jianxin
机构信息
State Key Laboratory of Genetic Engineering and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032, People's Republic of China.
出版信息
Biochem Biophys Res Commun. 2006 Jan 13;339(2):591-6. doi: 10.1016/j.bbrc.2005.11.054. Epub 2005 Nov 17.
ATF5 transcription factor plays an essential role in hematopoietic and glioma cell survival and neuronal cell differentiation. Here, we report for the first time the pro-apoptosis role of ATF5 and identify Cyclin D3 as an ATF5-targeted apoptosis-related gene. The ectopic expression of ATF5 in HeLa cells could markedly increase cisplatin-induced apoptosis and the cleavage of Caspase-3, and induce Cyclin D3 mRNA expression via cooperation with E2F1 transcription factor. Moreover, the interference of Cyclin D3 expression by transfection with Cyclin D3 RNAi could protect cells from ATF5-mediated apoptosis induced by cisplatin, indicating the contribution of Cyclin D3 in ATF5-mediated apoptosis. Taken together, these results suggest that ATF5 increases cisplatin-induced apoptosis through up-regulation of Cyclin D3 transcription, which elicits survival signals in HeLa cells.
ATF5转录因子在造血细胞和胶质瘤细胞存活以及神经元细胞分化中起着至关重要的作用。在此，我们首次报道了ATF5的促凋亡作用，并确定细胞周期蛋白D3是一个受ATF5靶向的凋亡相关基因。ATF5在HeLa细胞中的异位表达可显著增加顺铂诱导的细胞凋亡以及半胱天冬酶-3的切割，并通过与E2F1转录因子协同作用诱导细胞周期蛋白D3 mRNA表达。此外，通过转染细胞周期蛋白D3 RNAi干扰细胞周期蛋白D3的表达可保护细胞免受顺铂诱导的ATF5介导的细胞凋亡，这表明细胞周期蛋白D3在ATF5介导的细胞凋亡中发挥作用。综上所述，这些结果表明，ATF5通过上调细胞周期蛋白D3转录来增加顺铂诱导的细胞凋亡，而细胞周期蛋白D3转录在HeLa细胞中引发存活信号。
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