Abstract
Class-I MHC-restricted T-cell associated molecule (CRTAM) is a member of the Nectin-like adhesion molecule family. It is rapidly induced in NK, NKT and CD8(+) T cells. Interaction with its ligand Nectin-like 2 results in increased secretion of IFN-gamma by activated CD8(+) T lymphocytes. Through sequential bioinformatic analyses of the upstream region of the human CRTAM gene, we detected cis-elements potentially important for CRTAM gene transcription. Analyzing 2kb upstream from the ATG translation codon by mutation analysis in conjunction with luciferase reporter assays, electrophoretic mobility shify assay (EMSA) and supershift assays, we identified an AP-1 binding site, located at 1.4kb from the ATG translation codon of CRTAM gene as an essential element for CRTAM expression in activated but not resting human CD8(+) T cells. CRTAM expression was reduced in activated CD8(+) T cells treated with the JNK inhibitor SP600125, indicating that CRTAM expression is driven by the JNK-AP-1 signaling pathway. This study represents the first CRTAM gene promoter analysis in human T cells and indicates that AP-1 is a positive transcriptional regulator of this gene, a likely important finding because CRTAM has recently been shown to play a role in IFN-gamma and IL-17 production and T cell proliferation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anthracenes / pharmacology
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism*
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Cell Adhesion Molecule-1
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Cell Adhesion Molecules
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Cell Proliferation / drug effects
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / physiology*
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Humans
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Immunoglobulins / biosynthesis*
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Immunoglobulins / immunology
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Immunoglobulins / metabolism
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Interferon-gamma / immunology
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Interferon-gamma / metabolism
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Interleukin-17 / biosynthesis
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Interleukin-17 / immunology
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Jurkat Cells
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Lymphocyte Activation / drug effects
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Lymphocyte Activation / physiology
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MAP Kinase Kinase 4 / antagonists & inhibitors
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MAP Kinase Kinase 4 / immunology
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MAP Kinase Kinase 4 / metabolism
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Membrane Proteins / immunology
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Membrane Proteins / metabolism
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Response Elements / physiology*
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Transcription Factor AP-1 / immunology
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Transcription Factor AP-1 / metabolism*
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Transcription, Genetic / drug effects
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Transcription, Genetic / physiology*
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Tumor Suppressor Proteins / immunology
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Tumor Suppressor Proteins / metabolism
Substances
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Anthracenes
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CADM1 protein, human
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Cell Adhesion Molecule-1
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Cell Adhesion Molecules
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Immunoglobulins
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Interleukin-17
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Membrane Proteins
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Transcription Factor AP-1
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Tumor Suppressor Proteins
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class-I restricted T cell-associated molecule
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pyrazolanthrone
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Interferon-gamma
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MAP Kinase Kinase 4