Identification and Characterization of the Promoter of Fibroblast Activation Protein

Overview

Journal Front Biosci (Elite Ed)

Specialty Biology

Date 2010 Jun 3

PMID 20515787

Citations 19

Authors

Jiping Zhang

Matthildi Valianou

Jonathan D Cheng

Affiliations

Soon will be listed here.

Abstract

Fibroblast activation protein (FAP) is a type II integral membrane glycoprotein belonging to the serine protease family. It is selectively expressed by tumor stromal fibroblasts and transiently in the fibroblasts of healing wounds. FAP has been shown to modulate growth, differentiation, adhesion, and metastasis of tumor cells. Despite the importance of FAP in cancer, the mechanisms that govern its expression have not been defined. In this study, we determined the transcription start site of the FAP gene and identified a 2-kb segment with promoter activity in cells expressing FAP. Truncation of this fragment revealed that the core promoter activity resided in a 245-bp fragment surrounding the transcription start site. Electrophoretic mobility shift assay showed that EGR1 binds to the FAP promoter. Mutation of the EGR1 site within this fragment significantly decreased the promoter activity of FAP and eliminated EGR1 binding. Down-regulation of EGR1 resulted in a significant reduction in endogenous FAP mRNA expression. These findings identify the basal transcriptional requirements of FAP gene expression and show EGR1 is an important regulator of FAP expression.

Citing Articles

Fibroblast activation protein: Pivoting cancer/chemotherapeutic insight towards heart failure.

Gehris J, Ervin C, Hawkins C, Womack S, Churillo A, Doyle J Biochem Pharmacol. 2023; 219:115914.

PMID: 37956895 PMC: 10824141. DOI: 10.1016/j.bcp.2023.115914.

The Role and Application of Fibroblast Activating Protein.

Zhang X, Xiao W, Qian J, Yang W, Xu H, Xu X Curr Mol Med. 2023; 24(9):1097-1110.

PMID: 37259211 DOI: 10.2174/1566524023666230530095305.

Efficiency of Promoters of Human Genes and at Organism Level in a Model.

Selina P, Alekseenko I, Kurtova A, Pleshkan V, Voronezhskaya E, Demidyuk I Int J Mol Sci. 2023; 24(8).

PMID: 37108352 PMC: 10138699. DOI: 10.3390/ijms24087192.

Role and mechanism of fibroblast-activated protein-α expression on the surface of fibroblast-like synoviocytes in rheumatoid arthritis.

Wang Z, Wang J, Lan T, Zhang L, Yan Z, Zhang N Front Immunol. 2023; 14:1135384.

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Cell-specific expression of the gene is regulated by enhancer elements.

Antonova D, Gnatenko D, Kotova E, Pleshkan V, Kuzmich A, Didych D Front Mol Biosci. 2023; 10:1111511.

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