Identification and functional characterization of a novel binding site on TNF-α promoter

Speaker: 陳天文

Commentator: 楊倍昌 老師

Time: 13:00-14:00

Place: Room 601

Abstract

Tumor necrosis factor alpha (TNF-α) is a major cytokine of inflammation that is produced by macrophages, monocytes and other cells. The production of TNF-α is regulated by some transcription factors when lipopolysaccharide (LPS) is stimulated. LPS is a major component of the gram-negative bacterial outer membrane. Previous studies show that some transcription factors, such as NF-κB, Ets, NF-AT, activating protein 1 (AP-1), cAMP response element-binding protein, and signal transducers and activator of transcription (STAT1), bind to TNF-α promoter. In 1999, the authors find a novel human lipopolysaccharide-induced transcription factor, human lipopolysaccharide-induced TNF-α factor (hLITAF), that interact with a novel DNA-binding domain located from -550 to -487 in the human TNF-α promoter. In this paper, the authors apply footprinting to identify a sequence motif, CTCCC (-515 to -511), within the TNF-α promoter that binds to hLITAF, and also find the region of hLITAF (amino acids 165-180) which specifically mediates binding to hTNF-α promoter.

    These findings can help to clarify the detail mechanism of LPS stimulation/TNF-α production interaction that contributes to TNF-α regulation to design new pharmacological intervention to address TNF-related diseases.

Reference:

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2.          Shogo T., Thomas D., Lior S. and Salomon A. (1995) Lipopolysaccharide-inducible and salicylate-senstitive nuclear factor(s) on human tumor necrosis factor alpha promoter. Infect Immun, 63, 1529-1534

3.          Xiaoren T., Matthew F., and Salomon A. (2003) Identification and functional characterization of a novel binding site on TNF-α promoter. PNAS, 100, 4096-4101