title: Cutting Edge: Foxp1 Controls Naive CD8+ T Cell Quiescence by Simultaneously Repressing Key Pathways in Cellular Metabolism and Cell Cycle Progression.
abstract: Previously we have shown that transcription factor Foxp1 plays an essential role in maintaining naive T cell quiescence; in the absence of Foxp1, mature naive CD8(+) T cells proliferate in direct response to homeostatic cytokine IL-7. In this study, we report that the deletion of Foxp1 in naive CD8(+) T cells leads to enhanced activation of the PI3K/Akt/mammalian target of rapamycin signaling pathway and its downstream cell growth and metabolism targets in response to IL-7. We found that Foxp1 directly regulates PI3K interacting protein 1, a negative regulator of PI3K. Additionally, we found that deletion of Foxp1 in naive CD8(+) T cells results in increased expression levels of E2fs, the critical components for cell cycle progression and proliferation, in a manner that is not associated with increased phosphorylation of retinoblastoma protein. Taken together, our studies suggest that Foxp1 enforces naive CD8(+) T cell quiescence by simultaneously repressing key pathways in both cellular metabolism and cell cycle progression.
authors.affiliation: Department of Microbiology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35205; and.
authors.forename: Hairong
authors.initials: H
authors.lastname: Wei
authors.affiliation: Department of Microbiology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35205; and.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Geng
authors.affiliation: Department of Microbiology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35205; and.
authors.forename: Bi
authors.initials: B
authors.lastname: Shi
authors.affiliation: Department of Microbiology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35205; and.
authors.forename: Zhenghui
authors.identifier: 0000-0003-4894-9744
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Microbiology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35205; and.
authors.forename: Yin-Hu
authors.initials: YH
authors.lastname: Wang
authors.affiliation: Department of Microbiology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35205; and.
authors.forename: Anna C
authors.identifier: 0000-0002-5326-4996
authors.initials: AC
authors.lastname: Stevens
authors.affiliation: Department of Microbiology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35205; and.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Sprout
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Min
authors.identifier: 0000-0003-0081-0460
authors.initials: M
authors.lastname: Yao
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China hkwang@ips.ac.cn huihu@uab.edu.
authors.forename: Haikun
authors.identifier: 0000-0002-4714-4672
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Microbiology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35205; and hkwang@ips.ac.cn huihu@uab.edu.
authors.forename: Hui
authors.initials: H
authors.lastname: Hu
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D049109:Cell Proliferation; D051858:Forkhead Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006706:Homeostasis; D015851:Interleukin-7 / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D012097:Repressor Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D051858:Forkhead Transcription Factors; D015851:Interleukin-7; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D019869:Phosphatidylinositol 3-Kinases; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D058570:TOR Serine-Threonine Kinases; C432917:Foxp1 protein, mouse; C579635:Pik3ip1 protein, mouse; C546843:mTOR protein, mouse