Sirt1, p53, and p38MAPK are Crucial Regulators of Detrimental Phenotypes of Embryonic Stem Cells with Max Expression Ablation
Sirt1, p53, and p38MAPK are Crucial Regulators of Detrimental Phenotypes of Embryonic Stem Cells with Max Expression Ablation
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DOI：
10.1002/stem.1147
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发表时间：
2012-08-01
期刊：
影响因子：
5.2
通讯作者：
Okuda, Akihiko
中科院分区：
文献类型：
--
作者：
Hishida, Tomoaki;Nozaki, Yuriko;Okuda, Akihiko
c-Myc参与多种细胞过程，包括细胞周期控制、致瘤转化和体细胞重编程为诱导多能细胞。c-Myc也是胚胎干细胞（ESC）自我更新和多能性的重要调节剂。我们最近证明了Max基因的丢失，编码所有Myc家族蛋白质的最佳特征伴侣，导致ESCs中多能状态的丧失和广泛的细胞死亡，严格按照这个顺序。然而，负责这些表型的机制和分子在很大程度上仍然不清楚。在这里，我们表明，Sirt 1，p53和p38（MAPK）是至关重要的参与有害表型的最大无效的胚胎干细胞。此外，我们的分析表明，这些蛋白质在不同的水平上参与到另一个层次的途径，导致细胞死亡的最大空胚胎干细胞。干细胞2012; 30：1634-1644
c-Myc participates in diverse cellular processes including cell cycle control, tumorigenic transformation, and reprogramming of somatic cells to induced pluripotent cells. c-Myc is also an important regulator of self-renewal and pluripotency of embryonic stem cells (ESCs). We recently demonstrated that loss of the Max gene, encoding the best characterized partner for all Myc family proteins, causes loss of the pluripotent state and extensive cell death in ESCs strictly in this order. However, the mechanisms and molecules that are responsible for these phenotypes remain largely obscure. Here, we show that Sirt1, p53, and p38(MAPK) are crucially involved in the detrimental phenotype of Max-null ESCs. Moreover, our analyses revealed that these proteins are involved at varying levels to one another in the hierarchy of the pathway leading to cell death in Max-null ESCs. STEM CELLS 2012; 30: 1634-1644