title: Site-specific Disruption of the Oct4/Sox2 Protein Interaction Reveals Coordinated Mesendodermal Differentiation and the Epithelial-Mesenchymal Transition.
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.
authors.affiliation: From the College of Life Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Pan
authors.affiliation: From the College of Life Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Cang
authors.affiliation: the State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou, Zhejiang 310003, China.
authors.forename: Songsong
authors.initials: S
authors.lastname: Dan
authors.affiliation: From the College of Life Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, China.
authors.forename: Jingchao
authors.initials: J
authors.lastname: Li
authors.affiliation: From the College of Life Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, China, the State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou, Zhejiang 310003, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Cheng
authors.affiliation: the State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou, Zhejiang 310003, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Kang
authors.affiliation: the State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China, and.
authors.forename: Xiaotao
authors.initials: X
authors.lastname: Duan
authors.affiliation: the Department of Radiation Biology, City of Hope National Medical Center and Beckman Research Institute, Duarte, California 91010.
authors.forename: Binghui
authors.initials: B
authors.lastname: Shen
authors.affiliation: the State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou, Zhejiang 310003, China, yingjiewang@zju.edu.cn.
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Wang
mesh_terms: D001224:Aspartic Acid / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D006801:Humans; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D001224:Aspartic Acid; D008239:Lysine
keywords: cell signaling; differentiation; epithelial-mesenchymal transition (EMT); pluripotency; post-translational modification (PTM); stem cells; transcription factor; tumor cell biology