Akt-signal integration is involved in the differentiation of embryonal carcinoma cells.

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 K...

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Main Authors: Bo Chen, Zheng Xue, Guanghui Yang, Bingyang Shi, Ben Yang, Yuemin Yan, Xue Wang, Daishu Han, Yue Huang, Wenji Dong
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3675137?pdf=render
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spelling doaj-d4320da1fb724d12bf583239810637ea2020-11-25T00:18:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0186e6487710.1371/journal.pone.0064877Akt-signal integration is involved in the differentiation of embryonal carcinoma cells.Bo ChenZheng XueGuanghui YangBingyang ShiBen YangYuemin YanXue WangDaishu HanYue HuangWenji DongThe 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.http://europepmc.org/articles/PMC3675137?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Bo Chen
Zheng Xue
Guanghui Yang
Bingyang Shi
Ben Yang
Yuemin Yan
Xue Wang
Daishu Han
Yue Huang
Wenji Dong
spellingShingle Bo Chen
Zheng Xue
Guanghui Yang
Bingyang Shi
Ben Yang
Yuemin Yan
Xue Wang
Daishu Han
Yue Huang
Wenji Dong
Akt-signal integration is involved in the differentiation of embryonal carcinoma cells.
PLoS ONE
author_facet Bo Chen
Zheng Xue
Guanghui Yang
Bingyang Shi
Ben Yang
Yuemin Yan
Xue Wang
Daishu Han
Yue Huang
Wenji Dong
author_sort Bo Chen
title Akt-signal integration is involved in the differentiation of embryonal carcinoma cells.
title_short Akt-signal integration is involved in the differentiation of embryonal carcinoma cells.
title_full Akt-signal integration is involved in the differentiation of embryonal carcinoma cells.
title_fullStr Akt-signal integration is involved in the differentiation of embryonal carcinoma cells.
title_full_unstemmed Akt-signal integration is involved in the differentiation of embryonal carcinoma cells.
title_sort akt-signal integration is involved in the differentiation of embryonal carcinoma cells.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2013-01-01
description 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.
url http://europepmc.org/articles/PMC3675137?pdf=render
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