NDLI: Identification and functional characterization of a novel binding site on TNF-alpha promoter.

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

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Fenton, Matthew J. Amar, Salomon Tang, Xiaoren
Description	Author Affiliation: Tang X ( Department of Periodontology and Oral Biology, School of Dental Medicine, Boston University, Boston, MA 02118, USA.);
Abstract	Transcription of the tumor necrosis factor (TNF) gene is rapidly and transiently induced by lipopolysaccharide in cells of monocytemacrophage lineage. Previous studies have suggested that in the mouse, multiple NF-kappaBRel-binding sites contribute to the TNF transcriptional response to LPS. But the role of these regulatory elements in transcriptional activation of the TNF-alpha gene in human monocytes remains unclear. Previously, a transcription factor, termed lipopolysaccharide-induced TNF-alpha factor (LITAF), was found to regulate TNF-alpha gene expression. However, the specific protein domain(s) of human (h)LITAF that interact with the hTNF-alpha promoter had not been identified. In this study, we identify by footprinting a sequence motif, CTCCC (-515 to -511), within the TNF-alpha promoter that binds to hLITAF. We also identify the region of hLITAF (amino acids 165-180) that was named peptide B and specifically mediates binding to the hTNF-alpha promoter. When THP-1 cells were stimulated with this peptide B, it was sufficient to induce TNF-alpha secretion. Induction of TNF-alpha transcription by LPS or peptide B depended on the presence of the -515 to -511 promoter region, which was found to be essential for hLITAF binding. Together, these findings help to clarify the mechanism of hLITAFhTNF-alpha interaction and the manner by which hLITAF contributes to hTNF-alpha regulation in an attempt to design new pharmacological interventions to address TNF-related diseases.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	7
Volume Number	100
Language	English
Publisher	National Academy of Sciences
Publisher Date	2003-04-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Promoter Regions, Genetic Genetics Tumor Necrosis Factor-alpha Amino Acid Sequence Binding Sites Cell Line Cloning, Molecular DNA Footprinting DNA Primers Escherichia Coli Immunology Lipopolysaccharides Pharmacology Molecular Sequence Data Peptide Fragments Chemical Synthesis Chemistry Polymerase Chain Reaction Drug Effects TATA Box Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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