c-Myc is necessary for DNA damage-induced apoptosis in the G2 phase of the cell cycle
c-Myc is necessary for DNA damage-induced apoptosis in the G2 phase of the cell cycle
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DOI：
10.1128/mcb.21.15.4929-4937.2001
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发表时间：
2001-08-01
影响因子：
5.3
通讯作者：
Sedivy, JM
中科院分区：
文献类型：
--
作者：
Adachi, S;Obaya, AJ;Sedivy, JM
C-myc原癌基因编码一种转录因子，参与调节细胞的增殖、分化和凋亡。C-Myc的异位过表达已被证明可使细胞对凋亡敏感。我们在这里报道，由于c-myc基因被靶向同源重组破坏而导致c-Myc活性缺失的细胞，在细胞周期的G期中，DNA损伤启动的细胞凋亡是有缺陷的。C-Myc的下游效应因子是细胞周期蛋白A，其在c-myc(-/-)细胞中的异位表达挽救了细胞的凋亡缺陷。G_1反应的动力学表明，细胞周期蛋白A的诱导和伴随的CDK2的激活是细胞凋亡的早期阶段。而在c-myc(-/-)细胞中，细胞周期蛋白E和细胞周期蛋白D_1的表达不能挽救细胞的凋亡缺陷，细胞周期G_1期的凋亡过程不受影响。这些观察将DNA损伤诱导的细胞凋亡与细胞周期进展联系起来，并暗示c-Myc参与了这些途径的一部分的功能。
The c-myc proto-oncogene encodes a transcription factor that participates in the regulation of cellular proliferation, differentiation, and apoptosis. Ectopic overexpression of c-Myc has been shown to sensitize cells to apoptosis. We report here that cells lacking c-Myc activity due to disruption of the c-myc gene by targeted homologous recombination are defective in DNA damage-initiated apoptosis in the G, phase of the cell cycle. The downstream effector of c-Myc is cyclin A, whose ectopic expression in c-myc(-/-) cells rescues the apoptosis defect. The kinetics of the G, response indicate that the induction of cyclin A and the concomitant activation of Cdk2 represent an early step during commitment to apoptosis. In contrast, expression of cyclins E and D1 does not rescue the apoptosis defect, and apoptotic processes in G, phase are not affected in c-myc(-/-) cells. These observations link DNA damage-induced apoptosis with cell cycle progression and implicate c-Myc in the functioning of a subset of these pathways.