HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 277, Issue 28, 25329-25336, July 12, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/28/25329    most recent M203688200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Boffa, M. B. Articles by Koschinsky, M. L. Search for Related Content PubMed PubMed Citation Articles by Boffa, M. B. Articles by Koschinsky, M. L. Social Bookmarking                      What's this?

A Role for CCAAT/Enhancer-binding Protein in Hepatic Expression of Thrombin-activable Fibrinolysis Inhibitor^*

Michael B. Boffa, Jeffrey D. Hamill, Nazareth Bastajian, Rebecca Dillon, Michael E. Nesheim^§, and Marlys L. Koschinsky^¶

From the Departments of  Biochemistry and ^§ Medicine, Queen's University, Kingston, Ontario K7L 3N6, Canada

Thrombin-activable fibrinolysis inhibitor (TAFI) is a procarboxypeptidase B-like zymogen that upon activation by thrombin, thrombin-thrombomodulin, or plasmin attenuates fibrin clot lysis by inhibiting positive feedback in the fibrinolytic cascade. The concentration of TAFI in plasma varies in the human population and thus may constitute a risk factor for thrombotic disorders. In addition, TAFI has been reported to be a positive acute phase reactant in mice. We have initiated molecular analysis of the human TAFI promoter to understand the mechanisms underlying regulation of TAFI gene expression. We identified a putative C/EBP-binding site between 53 and 40 of the promoter. Mutations in this site that abolish C/EBP binding decrease TAFI promoter activity in human hepatoma (HepG2) cells by ~80%. Gel mobility shift analyses indicated that C/EBP- present in HepG2 nuclear extracts and C/EBP- and - present in adult rat liver nuclear extracts bind to the C/EBP site. C/EBP-, -, and - isoforms are all capable of binding to the C/EBP site and activating the TAFI promoter. The identification of a functional C/EBP-binding site in the human TAFI promoter may have important implications for the regulation of expression of this gene during development and in response to inflammatory stimuli.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				H. Schrem, J. Klempnauer, and J. Borlak Liver-Enriched Transcription Factors in Liver Function and Development. Part II: the C/EBPs and D Site-Binding Protein in Cell Cycle Control, Carcinogenesis, Circadian Gene Regulation, Liver Regeneration, Apoptosis, and Liver-Specific Gene Regulation Pharmacol. Rev., June 1, 2004; 56(2): 291 - 330. [Abstract] [Full Text] [PDF]

				M. B. Boffa, J. D. Hamill, D. Maret, D. Brown, M. L. Scott, M. E. Nesheim, and M. L. Koschinsky Acute Phase Mediators Modulate Thrombin-activable Fibrinolysis Inhibitor (TAFI) Gene Expression in HepG2 Cells J. Biol. Chem., March 7, 2003; 278(11): 9250 - 9257. [Abstract] [Full Text] [PDF]