title: Marked Reduction in FoxO1 Protein by its Enhanced Proteasomal Degradation in Zfat-deficient Peripheral T-Cells.
abstract: BACKGROUND
  Zfat is a nuclear protein that harbours putative DNA-binding domains. T-cell specific deletion of Zfat in Zfat(f/f)-CD4Cre mice yields a significant decrease in the number of peripheral T-cells with a lower surface expression of interleukin-7 receptor-α (IL-7Rα). However, the molecular mechanism by which Zfat controls IL-7Rα expression remains unknown.
  
  
  METHODS
  Expression levels of the molecules involved in IL-7Rα expression were determined by immunoblotting.
  
  
  RESULTS
  Zfat-deficient peripheral T-cells showed a marked reduction in the FoxO1 protein that regulates IL-7Rα expression; however, the FoxO1 mRNA expression level was not affected by Zfat-deficiency. Furthermore, treatment of Zfat-deficient T-cells with a proteasome inhibitor, epoxomicin, restored FoxO1 expression levels, indicating that the loss of Zfat enhanced the proteasomal degradation of the FoxO1 protein.
  
  
  CONCLUSIONS
  These results suggest that Zfat is required for peripheral T-cell homeostasis through IL-7Rα expression by controlling the FoxO1 protein.
authors.affiliation: Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Iwaihara
authors.affiliation: Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Ishikura
authors.affiliation: Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Doi
authors.affiliation: Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Tsunoda
authors.affiliation: Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fujimoto
authors.affiliation: Department of Laboratory Animal Medicine, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan Section of Animal Models, Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Okamura
authors.affiliation: Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka, Japan sshirasa@fukuoka-u.ac.jp.
authors.forename: Senji
authors.initials: S
authors.lastname: Shirasawa
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D053699:Interleukin-7 Receptor alpha Subunit / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009842:Oligopeptides / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D053699:Interleukin-7 Receptor alpha Subunit; D009842:Oligopeptides; D061988:Proteasome Inhibitors; D012333:RNA, Messenger; D014157:Transcription Factors; C529571:ZFAT protein, mouse; D046988:Proteasome Endopeptidase Complex; C078846:epoxomicin
keywords: FoxO1; IL-7Rα; T-cell homeostasis; Zfat; proteasomal degradation