title: Uhrf1 Controls iNKT Cell Survival and Differentiation through the Akt-mTOR Axis.
abstract: Uhrf1 (also known as Np95) is a regulator of DNA methylation and histone ubiquitination and plays an important role in embryogenesis and tumorigenesis. Here, we report that Uhrf1 is essential for invariant natural killer T (iNKT) cell development. We found that Uhrf1 was significantly upregulated in stage 1 iNKT cells. Targeted disruption of Uhrf1 resulted in stage 1-specific transition defects as observed by not only increased apoptosis, but also aberrant effector differentiation, which eventually led to the impaired generation of iNKT cells in Uhrf1-deficient mice. Notably, Uhrf1 deficiency resulted in attenuated activation of Akt-mTOR signaling in stage 1 iNKT cells and overexpression of active Akt rescued iNKT cell developmental defects. Collectively, our results suggest that Uhrf1 regulation of the Akt-mTOR signaling pathway is required for iNKT cell development.
authors.affiliation: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Xufeng
authors.initials: X
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Liu
authors.affiliation: CAS Key Laboratory of Innate Immunity and Chronic Disease, CAS Center for Excellence in Molecular Cell Science, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Li
authors.initials: L
authors.lastname: Bai
authors.affiliation: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Chenqi
authors.initials: C
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 200031, China. Electronic address: liux@sibs.ac.cn.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D002454:Cell Differentiation; D002470:Cell Survival; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000166:cytology* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000172:deficiency / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D009687:Nuclear Proteins; D044767:Ubiquitin-Protein Ligases; C117054:Uhrf1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases