A novel NF-kappaB binding site controls human granzyme B gene transcription.
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-kappaB-signaling pathway is involved in such control. Furthermore, a novel downstream human granzyme B gene sequence (GGAGATTCCC) was identified for NF-kappaB binding. EMSA, luciferase, and chromatin immunoprecipitation assays in vitro and in vivo indicated that this NF-kappaB 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-kappaB binding site, which plays a pivotal role in controlling human granzyme B gene transcription.
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, China.
Chunjian
C
Huang
Enguang
E
Bi
Yu
Y
Hu
Weiwen
W
Deng
Zhigang
Z
Tian
Chen
C
Dong
Yuanjie
Y
Hu
Bing
B
Sun
D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D053804:Granzymes; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000145:classification / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D012697:Serine Endopeptidases / Q000235:genetics*; D015398:Signal Transduction; D014158:Transcription, Genetic / Q000235:genetics*
D007376:Interleukin-2; D016328:NF-kappa B; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases