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B Binding Site Controls Human Granzyme B Gene Transcription1
* Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China;
School of Life Sciences, University of Science and Technology of China, Anhui, China;
Department of Immunology, M. D. Anderson Cancer Center, Houston, TX 77030;
Shanghai Biochip, Shanghai, China; and
¶
Immunology Division, E-Institutes of Shanghai Universities, Shanghai, China
Granzyme B expression is essential for eliciting NK cell cytotoxicity and T cell function. However, its transcriptional regulatory mechanism is not well understood. In this report, we demonstrate in human NK cells and T cells that the NF-
B-signaling pathway is involved in such control. Furthermore, a novel downstream human granzyme B gene sequence (GGAGATTCCC) was identified for NF-B binding. EMSA, luciferase, and chromatin immunoprecipitation assays in vitro and in vivo indicated that this NF-B binding site is functional in an NK cell line and its primary counterpart. Our data also demonstrate that this binding site is functional in Jurkat T cells. Taken together, we identified a novel NF-B binding site, which plays a pivotal role in controlling human granzyme B gene transcription.
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