Document Detail


Characterization of thrombomodulin expression in response to retinoic acid and identification of a retinoic acid response element in the human thrombomodulin gene.
MedLine Citation:
PMID:  8207015     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Thrombomodulin (TM) is an essential cofactor for the physiologic activation of the anticoagulant protein C by thrombin. We have observed that the expression of TM mRNA in response to retinoic acid was markedly increased in human U937 monoblast-like cells, and human MEG01 megakaryocyte-like cells, but not in human umbilical vein cells, murine hemangioma cells, human K562 erythroblast-like cells, and murine HSD fibroblast-like cells. TM activity in U937 cells and MEG01 cells was not detectable in untreated cells, but developed rapidly after treatment with retinoic acid. In endothelial cells there was minimal change in TM activity in response to retinoic acid treatment. We have isolated clones for the genes for murine and human TM and have identified potential retinoic acid response elements in the 5'-flanking region of the human gene. In U937 cells the increase in mRNA levels was associated with increased transcription, and transient transfection studies with reporter plasmids demonstrate functional retinoic acid response elements present in the 5'-flanking region of the gene. Deletion of, and mutations introduced into, the potential retinoic acid response element confirm the functional response in transient transfections.
Authors:
W A Dittman; S C Nelson; P K Greer; E T Horton; M L Palomba; S S McCachren
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  269     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1994 Jun 
Date Detail:
Created Date:  1994-07-14     Completed Date:  1994-07-14     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  16925-32     Citation Subset:  IM    
Affiliation:
Division of Hematology/Oncology, Durham Veterans Administration Medical Center, North Carolina.
Data Bank Information
Bank Name/Acc. No.:
GENBANK/M74231;  M74564
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MeSH Terms
Descriptor/Qualifier:
Animals
Base Sequence
Binding Sites
CHO Cells
Cell Line
Cricetinae
DNA / genetics,  metabolism
Hemangioma / metabolism
Hominidae / genetics*
Humans
Megakaryocytes / metabolism
Mice
Molecular Sequence Data
Promoter Regions, Genetic* / drug effects
Thrombomodulin / biosynthesis*,  genetics*
Transcription, Genetic
Transfection
Tretinoin / pharmacology*
Tumor Cells, Cultured
Umbilical Veins / metabolism
Grant Support
ID/Acronym/Agency:
P50-AR39162/AR/NIAMS NIH HHS; P50-HL26309-11/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Thrombomodulin; 302-79-4/Tretinoin; 9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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