Stem Cell：SIRT1，P53和p38MAPK调节Max缺失时ESC的死亡

Sirt1, p53 and p38MAPK are Crucial Regulators of Detrimental Phenotypes of ESCs with Max Expression Ablation?

Tomoaki Hishida1,5,?, Yuriko Nozaki1,5, Yutaka Nakachi2,3, Yosuke Mizuno3, Hiroyoshi Iseki3,5, Miyuki Katano1, Masayoshi

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 p38MAPK 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.