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

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2016 Jul 3

PMID 27369080

Citations 16

Authors

Xiao Pan

Xiaohui Cang

Songsong Dan

Jingchao Li

Jie Cheng

Bo Kang

Xiaotao Duan

Binghui Shen

Ying-Jie Wang

Affiliations

Soon will be listed here.

Abstract

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.

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