Characterization of CRTAM gene promoter: AP-1 transcription factor control its expression in human T CD8 lymphocytes

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-γ 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 2 kb 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 1.4 kb 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-γ and IL-17 production and T cell proliferation.