Division of Developmental Biology, Saitama Medical University, Hidaka, Saitama, Japan.
Stem Cells. 2012 Aug;30(8):1634-44. doi: 10.1002/stem.1147.
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.
c-Myc 参与多种细胞过程，包括细胞周期控制、肿瘤发生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（ESCs）自我更新和多能性的重要调节因子。我们最近证明，编码所有 Myc 家族蛋白最佳特征伴侣的 Max 基因的缺失，会导致 ESCs 严格按照这一顺序失去多能状态和广泛的细胞死亡。然而，导致这些表型的机制和分子在很大程度上仍不清楚。在这里，我们表明 Sirt1、p53 和 p38（MAPK）在 Max 缺失 ESCs 的有害表型中起着至关重要的作用。此外，我们的分析表明，这些蛋白质在导致 Max 缺失 ESCs 细胞死亡的途径的层次结构中彼此相互作用的程度不同。
