Vav‐induced activation of the human IFN‐γ gene promoter is mediated by upregulation of AP‐1 activity

FEBS Letters

Mori, Akio²  Elly, Chris³  Tanaka, Yoshihiko³  Kaminuma, Osamu¹  Altman, Amnon³  Liu, Yun-Cai³  Miyatake, Shoichiro¹ 

[1] Department of Immunology, The Tokyo Metropolitan Institute of Medical Science, 2-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan;Clinical Research Center for Allergy and Rheumatology, National Sagamihara Hospital, 18-1 Sakuradai, Sagamihara, Kanagawa 228-8533, Japan;Division of Cell Biology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA

关键词: Vav;    AP-1;    Interferon-γ;    NFAT;    Ying-Yang 1;    ATF;    activation transcription factor;    β-gal;    β-galactosidase;    EMSA;    electrophoresis mobility shift assay;    HA;    hemagglutinin;    GEF;    guanine nucleotide exchange factor;    GST;    glutathione S-transferase;    JNK;    c-Jun N-terminal kinase;    mAb;    monoclonal antibody;    TCR;    T cell receptor;    YY1;    Ying-Yang 1;   

DOI  :  10.1016/S0014-5793(02)02316-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The role of Vav in the transcriptional regulation of the human interferon-γ (IFN-γ) promoter was investigated. Overexpression of Vav in Jurkat-TAg cells enhanced T cell receptor (TCR)-induced activation of a luciferase (Luc) reporter gene construct driven by cis-regulatory element of the IFN-γ gene (−346 to +7). Electrophoresis mobility shift and Luc reporter assays demonstrated that the DNA-binding and transcriptional activity of the proximal AP-1-dependent NFAT site (positions −172 to −138), the AP-1/Ying-Yang 1 (YY1)-binding site (−209 to −184), and a consensus AP-1-binding site were upregulated by Vav. Vav enhanced TCR-induced activation of c-Jun N-terminal kinase (JNK) and its upstream regulator, Rho family GTPases. Finally, coexpression of a dominant-negative Rac1 mutant suppressed Vav-mediated upregulation of the transcriptional and DNA-binding activity of the proximal NFAT/AP-1 site and the AP-1/YY1 site, as well as the complete IFN-γ promoter activity. Vav activates the IFN-γ promoter via upregulation of AP-1-binding through a Rac1/JNK pathway.

【 授权许可】

Unknown