Akt-Signal Integration Is Involved in the Differentiation of Embryonal Carcinoma Cells

被引：37

作者：

Chen, Bo ^{[1
,2
]}

Xue, Zheng ^{[2
,3
,5
]}

Yang, Guanghui ^{[2
,3
,5
]}

Shi, Bingyang ^{[1
,2
]}

Yang, Ben ^{[1
,2
]}

Yan, Yuemin ^{[1
,2
]}

Wang, Xue ^{[2
,4
,5
]}

Han, Daishu ^{[1
,2
]}

Huang, Yue ^{[2
,4
,5
]}

Dong, Wenji ^{[1
,2
]}

机构：

[1] Chinese Acad Med Sci, Inst Basic Med Sci, Dept Cell Biol, Beijing 100730, Peoples R China

[2] Peking Union Med Coll, Beijing 100021, Peoples R China

[3] Chinese Acad Med Sci, Inst Basic Med Sci, Dept Biochem, Beijing 100730, Peoples R China

[4] Chinese Acad Med Sci, Inst Basic Med Sci, Dept Med Genet, Beijing 100730, Peoples R China

[5] Chinese Acad Med Sci, Inst Basic Med Sci, State Key Lab Med Mol Biol, Beijing 100730, Peoples R China

来源：

PLOS ONE | 2013年 / 8卷 / 06期

基金：

国家高技术研究发展计划(863计划);

关键词：

HEMATOPOIETIC STEM-CELLS; LEUKEMIA-INITIATING CELLS; NANOG EXPRESSION; F9; CELLS; SATB1; PHOSPHORYLATION; PLURIPOTENCY; QUIESCENCE; GROWTH; OCT4;

D O I：

10.1371/journal.pone.0064877

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The mechanism by which Akt modulates stem cell homeostasis is still incompletely defined. Here we demonstrate that Akt phosphorylates special AT-rich sequences binding protein 1 (SATB1) at serine 47 and protects SATB1 from apoptotic cleavage. Meanwhile, Akt phosphorylates Oct4 at threonine 228 and Klf4 at threonine 399, and accelerates their degradation. Moreover, PI3K/Akt signaling enhances the binding of SATB1 to Sox2, thereby probably impairing the formation of Oct4/Sox2 regulatory complexes. During retinoic acid (RA)-induced differentiation of mouse F9 embryonal carcinoma cells (ECCs), the Akt activation profile as well as its substrate spectrum is strikingly correlated with the down-regulation of Oct4, Klf4 and Nanog, which suggests Akt activation is coupled to the onset of differentiation. Accordingly, Akt-mediated phosphorylation is crucial for the capability of SATB1 to repress Nanog expression and to activate transcription of Bcl2 and Nestin genes. Taken together, we conclude that Akt is involved in the differentiation of ECCs through coordinated phosphorylations of pluripotency/differentiation factors.

引用

页数：15

共 37 条

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