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

作者: Bo Chen , Zheng Xue , Guanghui Yang , Bingyang Shi , Ben Yang

DOI: 10.1371/JOURNAL.PONE.0064877

关键词: PhosphorylationKLF4Cell biologyPI3K/AKT/mTOR pathwayCellular differentiationAKT1Molecular biologyHomeobox protein NANOGSOX2BiologyProtein kinase BGeneral Biochemistry, Genetics and Molecular BiologyGeneral Agricultural and Biological SciencesGeneral Medicine

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

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