A Novel NF-B Binding Site Controls Human Granzyme B Gene Transcription

Authors:
Huang C, Bi E, Hu Y, Deng W, Tian Z, Dong C, Hu Y, Sun B
In:
Source: J Immunol
Publication Date: (2006)
Issue: 176(7): 4173-81
Research Area:
Immunotherapy / Hematology
Cells used in publication:
Jurkat
Species: human
Tissue Origin: blood
Jurkat-modified
Species: human
Tissue Origin:
NK-92
Species: human
Tissue Origin: blood
Platform:
Nucleofectorâ„¢ I/II/2b
Abstract
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.