Reciprocal Regulation of Akt and Oct4 Promotes the Self-Renewal and Survival of Embryonal Carcinoma Cells
作者： Yuanji Lin , Ying Yang , Weihua Li , Qi Chen , Jie Li
DOI: 10.1016/J.MOLCEL.2012.08.030
关键词:
摘要: Signaling via the Akt serine/threonine protein kinase plays critical roles in self-renewal of embryonic stem cells and their malignant counterpart, embryonal carcinoma (ECCs). Here we show that ECCs, phosphorylated master pluripotency factor Oct4 at threonine 235, levels ECCs correlated with resistance to apoptosis tumorigenic potential. Phosphorylation increased its stability facilitated nuclear localization interaction Sox2, which promoted transcription core stemness genes POU5F1 NANOG. Furthermore, unphosphorylated bound AKT1 promoter repressed transcription. by resulted dissociation from promoter, activated cell survival. Therefore, a site-specific, posttranslational modification orchestrates regulation stability, subcellular localization, transcriptional activities, collectively promotes survival tumorigenicity ECCs.
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sci-hub.se 参考文章(55)
Ying Liu, Soojung Shin, Xianmin Zeng, Ming Zhan, Rodolfo Gonzalez, Franz-Josef Mueller, Catherine M Schwartz, Haipeng Xue, Huai Li, Shawn C Baker, Eugene Chudin, David L Barker, Timothy K McDaniel, Steffen Oeser, Jeanne F Loring, Mark P Mattson, Mahendra S Rao, Genome wide profiling of human embryonic stem cells (hESCs), their derivatives and embryonal carcinoma cells to develop base profiles of U.S. Federal government approved hESC lines. BMC Developmental Biology. ,vol. 6, pp. 20- 20 ,(2006) , 10.1186/1471-213X-6-20
Christine E. Eyler, Wen-Chi Foo, Katherine M. LaFiura, Roger E. McLendon, Anita B. Hjelmeland, Jeremy N. Rich, Brain Cancer Stem Cells Display Preferential Sensitivity to Akt Inhibition Stem Cells. ,vol. 26, pp. 3027- 3036 ,(2008) , 10.1634/STEMCELLS.2007-1073
Hitoshi Niwa, Jun-ichi Miyazaki, Austin G. Smith, Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nature Genetics. ,vol. 24, pp. 372- 376 ,(2000) , 10.1038/74199
Zhao Wu, Wei Zhang, Guibin Chen, Lu Cheng, Jing Liao, Nannan Jia, Yuan Gao, Huiming Dai, Jinduo Yuan, Linzhao Cheng, Lei Xiao, Combinatorial signals of activin/nodal and bone morphogenic protein regulate the early lineage segregation of human embryonic stem cells. Journal of Biological Chemistry. ,vol. 283, pp. 24991- 25002 ,(2008) , 10.1074/JBC.M803893200
Pearl A. Campbell, Carolina Perez-Iratxeta, Miguel A. Andrade-Navarro, Michael A. Rudnicki, Oct4 Targets Regulatory Nodes to Modulate Stem Cell Function PLoS ONE. ,vol. 2, pp. e553- ,(2007) , 10.1371/JOURNAL.PONE.0000553
Attila Reményi, Hans R Schöler, Matthias Wilmanns, Combinatorial control of gene expression Nature Structural & Molecular Biology. ,vol. 11, pp. 812- 815 ,(2004) , 10.1038/NSMB820
Amancio Carnero, The PKB/AKT pathway in cancer. Current Pharmaceutical Design. ,vol. 16, pp. 34- 44 ,(2010) , 10.2174/138161210789941865
Brendan D. Manning, Lewis C. Cantley, AKT/PKB signaling: navigating downstream. Cell. ,vol. 129, pp. 1261- 1274 ,(2007) , 10.1016/J.CELL.2007.06.009
Zheng Wang, Efrat Oron, Brynna Nelson, Spiro Razis, Natalia Ivanova, Distinct lineage specification roles for NANOG, OCT4, and SOX2 in human embryonic stem cells Cell Stem Cell. ,vol. 10, pp. 440- 454 ,(2012) , 10.1016/J.STEM.2012.02.016
Junlin Li, Binhua P Zhou, Activation of β-catenin and Akt pathways by Twist are critical for the maintenance of EMT associated cancer stem cell-like characters BMC Cancer. ,vol. 11, pp. 49- 49 ,(2011) , 10.1186/1471-2407-11-49