Functional analysis of the human tissue factor promoter and induction by serum

Journal Article · Thu Mar 01 04:00:00 EST 1990 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.87.6.2254· OSTI ID:6171623

Mackman, N; Fowler, B J; Edgington, T S; Morrissey, J H ^[1]

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1. Research Institute of Scripps Clinic, La Jolla, CA (USA)

Tissue factor (TF) is the primary initiator of the coagulation protease cascades. This cell surface glycoprotein is the receptor and essential cofactor for the serine protease factor VIIa. TF is constitutively expressed in some extravascular cell types and is transiently induced in monocytes, endothelial cells, and fibroblasts. Inducible expression is implicated in cellular immune responses, inflammation, and intravascular coagulation. Transcriptional regulation of the TF promoter was analyzed in COS-7 cells under conditions of (i) high-level expression and (ii) serum induction. The region comprising nucleotides-209 to + 121 supports high-level transcriptional activity and can be divided into two distinct regions: a region that exhibited low promoter activity and a region that enhanced transcriptional activity to a high level. The role of further upstream sequences is still to be established, although two consensus binding sites for the transcriptional activator protein AP-1 did enhance low-level promoter activity. In serum-starved COS-7 cells TF expression was transiently increased 20-fold by serum. All transcriptionally active constructs were responsive to serum, indicating the presence of at least one serum response element, whose function was retained in the immediate 5{prime} aspect of the gene. Based on this functional map, the authors propose that the elaborate pattern of TF expression by cells results from a relatively complex promoter.

• OSTI ID: 6171623
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 87:6; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BLOOD COAGULATION
CELL CONSTITUENTS
CHEMICAL REACTIONS
CROSS-LINKING
DAYS LIVING RADIOISOTOPES
DNA HYBRIDIZATION
DNA SEQUENCING
ENZYMES
GENE REGULATION
GENE REPRESSORS
GLYCOPROTEINS
HYBRIDIZATION
HYDROLASES
ISOTOPES
LIGHT NUCLEI
NUCLEI
NUCLEOPROTEINS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PEPTIDE HYDROLASES
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PLASMIDS
POLYMERIZATION
PROTEINS
RADIOISOTOPES
SERINE PROTEINASES
STRUCTURAL CHEMICAL ANALYSIS
TRANSCRIPTION