近日,，Stem Cell雜志在線報道了c-Myc基因重要伙伴蛋白Max基因缺失條件下胚胎干細胞喪失多能性并發(fā)生細胞死亡的機制研究進展,。
c-Myc基因參與多種細胞過程，包括細胞周期調控,，致瘤性轉化和體細胞重編程為誘導多能干細胞,。 c-Myc基因也是一個重要的調節(jié)自我更新和胚胎干細胞（ESCs）全能性的調節(jié)因子。
以往研究證實,，Max基因（該基因編碼Myc家族蛋白的最為人們熟知的合作伙伴因子）的缺失,，首先導致胚胎干細胞的多能性的喪失，隨后引起廣泛的細胞死亡,。
然而,，負責這些表型的分子機制仍然在很大程度上模糊不清。本研究表明,，SIRT1,，P53和p38MAPK在導致Max基因缺失胚胎干細胞這些破壞性表型過程中，發(fā)揮重要作用,。此外,，研究者的分析顯示，這些蛋白質在導致Max基因缺失胚胎干細胞細胞死亡的分子信號途徑的不同層次,，以不同水平互相作用,。(生物谷bioon.com)
doi:10.1016/j.cell.2011.10.017
PMC:
PMID:
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.
