Acetylation‐dependent regulation of essential iPS‐inducing factors: a regulatory crossroad for pluripotency and tumorigenesis

Cancer Medicine

Xiangpeng Dai¹  Pengda Liu¹  Alan W. Lau¹  Yueyong Liu¹ 

[1] Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts

关键词: Akt;    iPS cell;    Klf4;    Oct4;    p300;    Sox2;   

DOI  :  10.1002/cam4.298

来源: Wiley

【 摘 要 】

Abstract

Induced pluripotent stem (iPS) cells can be generated from somatic cells by coexpression of four transcription factors: Sox2, Oct4, Klf4, and c-Myc. However, the low efficiency in generating iPS cells and the tendency of tumorigenesis hinder the therapeutic applications for iPS cells in treatment of human diseases. To this end, it remains largely unknown how the iPS process is subjected to regulation by upstream signaling pathway(s). Here, we report that Akt regulates the iPS process by modulating posttranslational modifications of these iPS factors in both direct and indirect manners. Specifically, Akt directly phosphorylates Oct4 to modulate the Oct4/Sox2 heterodimer formation. Furthermore, Akt either facilitates the p300-mediated acetylation of Oct4, Sox2, and Klf4, or stabilizes Klf4 by inactivating GSK3, thus indirectly modulating stemness. As tumorigenesis shares possible common features and mechanisms with iPS, our study suggests that Akt inhibition might serve as a cancer therapeutic approach to target cancer stem cells.

【 授权许可】

CC BY   
© 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.