p53 and p73 Regulate Apoptosis but Not Cell-Cycle Progression in Mouse Embryonic Stem Cells upon DNA Damage and Differentiation.
p53 and p73 Regulate Apoptosis but Not Cell-Cycle Progression in Mouse Embryonic Stem Cells upon DNA Damage and Differentiation.
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p53 和 p73 在 DNA 损伤和分化时调节小鼠胚胎干细胞的细胞凋亡，但不调节细胞周期进展
DOI：
10.1016/j.stemcr.2016.10.008
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发表时间：
2016-12-13
影响因子：
5.9
通讯作者：
Xiao, Zhi-Xiong
中科院分区：
文献类型：
--
作者：
He, Hanbing;Wang, Cheng;Dai, Qian;Li, Fengtian;Bergholz, Johann;Li, Zhonghan;Li, Qintong;Xiao, Zhi-Xiong
胚胎干细胞（ESCs）是能够分化成所有体细胞类型的快速增殖细胞。在体细胞中，有充分的证据表明，p53在DNA损伤后迅速激活，以阻止细胞周期并诱导细胞凋亡。在小鼠胚胎干细胞中，p53也可以被功能性激活，但确切的生物学后果还没有得到很好的表征。在这里，我们证明了阿霉素治疗最初导致ESCs细胞周期停滞在G2/M，随后发生大量凋亡。G2/M期阻滞不需要p53或其靶基因p73。相反，p53和p73完全负责细胞凋亡。p53和p73也是小鼠胚胎干细胞分化诱导凋亡所必需的。此外，阿霉素治疗诱导视网膜母细胞瘤蛋白的表达在p53依赖性的方式。因此，p53和p73在由DNA损伤和分化诱导的凋亡中是关键的。p53/p73是mESC中DNA损伤诱导的细胞凋亡而不是G2/M停滞的关键p53和p73都是mESC中分化诱导的细胞凋亡所需的阿霉素通过p53介导的miR-17-92和miR-106 a-363的抑制诱导RB。在这篇文章中，Xiao，Li，P53和P73在DNA损伤诱导的细胞凋亡中起关键作用，但在mESCs的G2/M期阻滞中不起作用。此外，阿霉素通过p53介导的miR-17-92和miR-106 a-363抑制诱导RB。在分化过程中，p73而不是p53被诱导，并且p53和p73对于分化诱导的细胞凋亡都是关键的。
Embryonic stem cells (ESCs) are fast proliferating cells capable of differentiating into all somatic cell types. In somatic cells, it is well documented that p53 is rapidly activated upon DNA damage to arrest the cell cycle and induce apoptosis. In mouse ESCs, p53 can also be functionally activated, but the precise biological consequences are not well characterized. Here, we demonstrated that doxorubicin treatment initially led to cell-cycle arrest at G2/M in ESCs, followed by the occurrence of massive apoptosis. Neither p53 nor its target gene p73 was required for G2/M arrest. Instead, p53 and p73 were fully responsible for apoptosis. p53 and p73 were also required for differentiation-induced apoptosis in mouse ESCs. In addition, doxorubicin treatment induced the expression of retinoblastoma protein in a p53-dependent manner. Therefore, both p53 and p73 are critical in apoptosis induced by DNA damage and differentiation. p53/p73 are key for DNA damage-induced apoptosis but not G2/M arrest in mESCs Both p53 and p73 are required for differentiation-induced apoptosis in mESCs Doxorubicin induces RB via p53-mediated suppression of miR-17-92 and miR-106a-363 p73 expression is induced upon differentiation in mESCs In this article, Xiao, Li, and colleagues show that p53 and p73 are pivotal for DNA-damage-induced apoptosis but not for G2/M arrest in mESCs. In addition, doxorubicin induces RB via p53-mediated suppression of miR-17-92 and miR-106a-363. During differentiation, p73, but not p53, is induced, and both p53 and p73 are critical for differentiation-induced apoptosis.
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