NF‐κB and AP‐1 regulate activation‐dependent CD137 (4‐1BB) expression in T cells

FEBS Letters

Baek, Kyoung-Min¹  Kang, Chang-Yuil¹  Kim, Ho Won¹  Kim, Jae-Ouk¹ 

[1] Laboratory of Immunology and Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea

关键词: 4-1BB;    CD137;    T cell activation;    T cell receptor signal;    Transcription factor;    TNF;    tumor necrosis factor;    TCR;    T cell receptor;    AP-1;    activating protein-1;    NFAT;    nuclear factor of activated T cells;    P/I;    phorbol myristate acetate and ionomycin;    mAb;    monoclonal antibody;    β-gal;    β-galactosidase;   

DOI  :  10.1016/S0014-5793(03)00326-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown