title: Cutting edge: Expression of the transcription factor E74-like factor 4 is regulated by the mammalian target of rapamycin pathway in CD8+ T cells.
abstract: T cell receptor activation inhibits expression of the E74-like factor (ELF) 4 and Krüppel-like factor 4 genes to release naive CD8(+) T cells from their quiescent state. In this study, we show that ELF4 controls the ERK-mediated proliferative response by maintaining normal levels of dual-specificity phosphatases 1 and 5 in CD8(+) T cells. In activated CD8(+) T cells, the mammalian target of rapamycin pathway inhibits ELF4 and Krüppel-like factor 4 expression downstream of ERK and PI3K signaling. Our findings demonstrate that rapamycin could be used to modulate expression of this transcriptional network involved in cell-cycle regulation.
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamada
authors.forename: Kirsten
authors.initials: K
authors.lastname: Gierach
authors.forename: Ping-Hsien
authors.initials: PH
authors.lastname: Lee
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wang
authors.forename: H Daniel
authors.initials: HD
authors.lastname: Lacorazza
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000276:immunology*; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism*; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000276:immunology / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C491779:Elf4 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D014157:Transcription Factors; C546843:mTOR protein, mouse; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases
references.citation: Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7686-9
references.pmid: 7644477
references.citation: Nat Immunol. 2009 Jun;10(6):618-26
references.pmid: 19412182
references.citation: J Immunol. 2006 Dec 1;177(11):7497-504
references.pmid: 17114416
references.citation: Nat Immunol. 2001 Aug;2(8):698-704
references.pmid: 11477405
references.citation: Mol Cell. 2002 Nov;10(5):1071-81
references.pmid: 12453415
references.citation: J Biol Chem. 2008 Jun 20;283(25):17362-9
references.pmid: 18430737
references.citation: Nature. 2009 Jul 2;460(7251):103-7
references.pmid: 19494812
references.citation: Immunol Rev. 2009 Mar;228(1):41-57
references.pmid: 19290920
references.citation: Nat Rev Immunol. 2008 May;8(5):380-90
references.pmid: 18421304
references.citation: Annu Rev Pathol. 2009;4:175-98
references.pmid: 18783329
references.citation: Biochem J. 2009 Mar 15;418(3):475-89
references.pmid: 19228121
references.citation: Nat Immunol. 2008 May;9(5):513-21
references.pmid: 18391955
references.citation: Immunity. 2009 Mar 20;30(3):358-71
references.pmid: 19285438
references.citation: Nature. 2009 Jul 2;460(7251):108-12
references.pmid: 19543266
references.citation: Mol Immunol. 2006 Feb;43(6):754-62
references.pmid: 16360020
references.citation: Cancer Cell. 2006 Mar;9(3):175-87
references.pmid: 16530702
references.citation: J Biol Chem. 2009 Nov 6;284(45):30815-24
references.pmid: 19748894
references.citation: Nat Rev Immunol. 2009 May;9(5):324-37
references.pmid: 19390566
references.citation: J Immunol. 1996 Feb 1;156(3):1020-9
references.pmid: 8557975
references.citation: Nat Immunol. 2001 Dec;2(12):1174-82
references.pmid: 11694881