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NF‐κB and AP‐1 regulate activation‐dependent CD137 (4‐1BB) expression in T cells
Author(s) -
Kim Jae-Ouk,
Kim Ho Won,
Baek Kyoung-Min,
Kang Chang-Yuil
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)00326-0
Subject(s) - cd137 , microbiology and biotechnology , chemistry , nfkb1 , biology , transcription factor , biochemistry , cytotoxic t cell , in vitro , gene
4‐1BB(CD137) is a member of the tumor necrosis factor receptor superfamily and provides a costimulatory signal by interaction with 4‐1BB ligand expressed on antigen‐presenting cells. The expression of 4‐1BB is known to be activation‐dependent. Here, we investigated the transcriptional machinery required for T cell receptor (TCR) activation‐dependent induction of 4‐1BB expression in CD3‐CEM cells treated with phorbol myristate acetate and ionomycin. Using 5′‐deletion constructs of 4‐1BB promoter in luciferase reporter assays, we demonstrated that the transcriptional elements mediating 4‐1BB upregulation were located in the region between ∼0.9 and ∼1.1 kb from the translational start site. Characterization of these sites by electrophoretic mobility shift assay and site‐directed mutagenesis revealed that nuclear factor κB (NF‐κB) and activating protein‐1 (AP‐1) are involved. MEK and c‐Jun N‐terminal kinase‐1 activity was required for activation‐dependent 4‐1BB upregulation. Thus, NF‐κB and AP‐1 are involved in the TCR stimulation‐dependent transcriptional regulation of the 4‐1BB promoter.