Cutting edge: Expression of the transcription factor E74-like factor 4 is regulated by the mammalian target of rapamycin pathway in CD8+ T cells.
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.
Yamada
Takeshi
T
Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
Gierach
Kirsten
K
Lee
Ping-Hsien
PH
Wang
Xiaohong
X
Lacorazza
H Daniel
HD
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*
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
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