title: Reciprocal regulation of Akt and Oct4 promotes the self-renewal and survival of embryonal carcinoma cells.
abstract: Signaling via the Akt serine/threonine protein kinase plays critical roles in the self-renewal of embryonic stem cells and their malignant counterpart, embryonal carcinoma cells (ECCs). Here we show that in ECCs, Akt phosphorylated the master pluripotency factor Oct4 at threonine 235, and that the levels of phosphorylated Oct4 in ECCs correlated with resistance to apoptosis and tumorigenic potential. Phosphorylation of Oct4 increased its stability and facilitated its nuclear localization and its interaction with Sox2, which promoted the transcription of the core stemness genes POU5F1 and NANOG. Furthermore, in ECCs, unphosphorylated Oct4 bound to the AKT1 promoter and repressed its transcription. Phosphorylation of Oct4 by Akt resulted in dissociation of Oct4 from the AKT1 promoter, which activated AKT1 transcription and promoted cell survival. Therefore, a site-specific, posttranslational modification of the Oct4 protein orchestrates the regulation of its stability, subcellular localization, and transcriptional activities, which collectively promotes the survival and tumorigenicity of ECCs.
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou, Zhejiang 310003, China.
authors.forename: Yuanji
authors.initials: Y
authors.lastname: Lin
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.forename: Weihua
authors.initials: W
authors.lastname: Li
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Xiao
authors.initials: X
authors.lastname: Pan
authors.forename: Lina
authors.initials: L
authors.lastname: Zhou
authors.forename: Changwei
authors.initials: C
authors.lastname: Liu
authors.forename: Chunsong
authors.initials: C
authors.lastname: Chen
authors.forename: Jianqin
authors.initials: J
authors.lastname: He
authors.forename: Hongcui
authors.initials: H
authors.lastname: Cao
authors.forename: Hangping
authors.initials: H
authors.lastname: Yao
authors.forename: Li
authors.initials: L
authors.lastname: Zheng
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Xu
authors.forename: Zongping
authors.initials: Z
authors.lastname: Xia
authors.forename: Jiangtao
authors.initials: J
authors.lastname: Ren
authors.forename: Lei
authors.initials: L
authors.lastname: Xiao
authors.forename: Lanjuan
authors.initials: L
authors.lastname: Li
authors.forename: Binghui
authors.initials: B
authors.lastname: Shen
authors.forename: Honglin
authors.initials: H
authors.lastname: Zhou
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D018236:Carcinoma, Embryonal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D054278:Embryonal Carcinoma Stem Cells / Q000378:metabolism / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D050814:Octamer Transcription Factor-3 / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt