title: G0S2 modulates homeostatic proliferation of naïve CD8⁺ T cells and inhibits oxidative phosphorylation in mitochondria.
abstract: Since its discovery, diverse functions have been attributed to the G0/G1 switch gene 2 (G0S2), from lipid metabolism to control of cell proliferation. Our group showed for the first time that G0S2 promotes quiescence in hematopoietic stem cells by interacting with and retaining nucleolin around the nucleus. Herein, we report the role of G0S2 in the differentiation and function of CD8(+) T cells examined in mice with an embryonic deletion of the G0s2 gene. G0S2 expression in naïve CD8(+) T cells decreased immediately after T-cell receptor activation downstream of the mitogen-activated protein kinase, calcium/calmodulin, phosphatidylinositol 3'-kinase and mammalian target of rapamycin pathways. Surprisingly, G0S2-null naïve CD8(+) T cells displayed increased basal and spare respiratory capacity that was not associated with increased mitochondrial biogenesis but with increased phosphorylation of AMP-activated protein kinase α. Naïve CD8(+) T cells showed increased proliferation in response to in vitro activation and in vivo lymphopenia; however, naïve CD8(+) T cells expressing the OT-1 transgene exhibited normal differentiation of naïve cells to effector and memory CD8(+) T cells upon infection with Listeria monocytogenes in a wild-type or a G0s2-null environment, with increased circulating levels of free fatty acids. Collectively, our results suggest that G0S2 inhibits energy production by oxidative phosphorylation to fine-tune proliferation in homeostatic conditions.
authors: Department of Pathology and Immunology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA.
authors: Ping-Hsien
authors: PH
authors: Lee
authors: Department of Pathology and Immunology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA.
authors: Takeshi
authors: T
authors: Yamada
authors: Department of Pathology and Immunology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA.
authors: Chun Shik
authors: CS
authors: Park
authors: Department of Pathology and Immunology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA.
authors: Ye
authors: Y
authors: Shen
authors: Department of Pathology and Immunology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA.
authors: Monica
authors: M
authors: Puppi
authors: 1] Department of Pathology and Immunology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA [2] Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA.
authors: H Daniel
authors: HD
authors: Lacorazza
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002455:Cell Division; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D017930:Genes, Reporter; D006706:Homeostasis; D008089:Listeria monocytogenes; D008088:Listeriosis / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008231:Lymphopenia / Q000276:immunology / Q000378:metabolism; D038041:Lymphopoiesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction; D013047:Specific Pathogen-Free Organisms
chemical_list: D018797:Cell Cycle Proteins; D005230:Fatty Acids, Nonesterified; C508072:G0S2 protein, mouse; D011948:Receptors, Antigen, T-Cell; D017868:Cyclic AMP-Dependent Protein Kinases