Open AccessAcetylation‐dependent regulation of essential iPS ‐inducing factors: a regulatory crossroad for pluripotency and tumorigenesis
Author(s) -
Dai Xiangpeng,
Liu Pengda,
Lau Alan W.,
Liu Yueyong,
Inuzuka Hiroyuki
Publication year - 2014
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.298
Subject(s) - sox2 , klf4 , induced pluripotent stem cell , protein kinase b , carcinogenesis , microbiology and biotechnology , biology , acetylation , transcription factor , stem cell , somatic cell , cancer research , embryonic stem cell , signal transduction , cancer , genetics , gene
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.