NDLI: Site-specific Disruption of the Oct4/Sox2 Protein Interaction Reveals Coordinated Mesendodermal Differentiation and the Epithelial-Mesenchymal Transition

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Site-specific Disruption of the Oct4/Sox2 Protein Interaction Reveals Coordinated Mesendodermal Differentiation and the Epithelial-Mesenchymal Transition

Content Provider	Scilit
Author	Pan, Xiao Cang, Xiaohui Dan, Songsong Li, Jingchao Cheng, Jie Kang, Bo Duan, Xiaotao Shen, Binghui Wang, Ying-Jie
Copyright Year	2016
Description	Journal: Journal of Biological Chemistry Although the Oct4/Sox2 complex is crucial for maintaining the pluripotency of stem cells, the molecular basis underlying its regulation during lineage-specific differentiation remains unknown. Here, we revealed that the highly conserved Oct4/Lys-156 is important for maintaining the stability of the Oct4 protein and the intermolecular salt bridge between Oct4/Lys-151 and Sox2/Asp-107 that contributes to the Oct4/Sox2 interaction. Post-translational modifications at Lys-156 and K156N, a somatic mutation detected in bladder cancer patients, both impaired the Lys-151–Asp-107 salt bridge and the Oct4/Sox2 interaction. When produced as a recombinant protein or overexpressed in pluripotent stem cells, Oct4/K156N, with reduced binding to Sox2, significantly down-regulated the stemness genes that are cooperatively controlled by the Oct4/Sox2 complex and specifically up-regulated the mesendodermal genes and the SNAIL family genes that promote the epithelial-mesenchymal transition. Thus, we conclude that Oct4/Lys-156-modulated Oct4/Sox2 interaction coordinately controls the epithelial-mesenchymal transition and mesendoderm specification induced by specific differentiation signals.
Related Links	http://www.jbc.org/content/291/35/18353.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5000082/pdf http://www.jbc.org/article/S0021925820321979/pdf
Ending Page	18369
Page Count	17
Starting Page	18353
ISSN	00219258
e-ISSN	1083351X
DOI	10.1074/jbc.m116.745414
Journal	Journal of Biological Chemistry
Issue Number	35
Volume Number	291
Language	English
Publisher	Elsevier BV
Publisher Date	2016-08-01
Access Restriction	Open
Subject Keyword	Journal: Journal of Biological Chemistry Biochemistry and Molecular Biology Epithelial-mesenchymal Transition (emt) Post-translational Modification (ptm) Transcription Factor Tumor Cell Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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