Document Detail


Retinoic acid activation and thyroid hormone repression of the human alcohol dehydrogenase gene ADH3.
MedLine Citation:
PMID:  1321136     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mammalian alcohol dehydrogenase (ADH) catalyzes the oxidation of retinol to retinaldehyde, the rate-limiting step in the synthesis of retinoic acid. There exists a family of ADH isozymes encoded by unique genes, and it is unclear which isozymes are most important for regulation of retinoic acid synthesis during differentiation or development. A region in the human ADH3 promoter from -328 to -272 base pairs was shown previously to function as a retinoic acid response element (RARE), prompting an hypothesis for a positive feedback mechanism controlling retinoic acid synthesis (Duester, G., Shean, M. L., McBride, M. S., and Stewart, M. J. (1991) Mol. Cell. Biol. 11, 1638-1646). The ADH3 RARE contains three direct AGGTCA repeats which constitute the critical nucleotides of RAREs present in other genes. We dissected the ADH3 RARE and determined that receptor binding as well as transactivation are dependent upon only the two downstream AGGTCA motifs separated by 5 base pairs, a structure noticed previously for a RARE in the promoter for the retinoic acid receptor beta (RAR beta) gene. ADH3 and RAR beta RAREs functioned similarly in transfection assays, suggesting that the feedback mechanisms controlling ADH3 and RAR beta utilize a common RARE. We also found that the normal functioning of the ADH3 RARE was abrogated by thyroid hormone receptor in the presence of thyroid hormone. A negative thyroid hormone response element in the human ADH3 promoter was found to colocalize with the RARE. Since ADH production in rat liver is known to be repressed by thyroid hormone, these findings suggest that human ADH production may also be subject to thyroid hormone repression and that the mechanism involves an interference with retinoic acid induction.
Authors:
P P Harding; G Duester
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  267     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1992 Jul 
Date Detail:
Created Date:  1992-08-14     Completed Date:  1992-08-14     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:  14145-50     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, Colorado State University, Fort Collins 80523.
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MeSH Terms
Descriptor/Qualifier:
Alcohol Dehydrogenase / biosynthesis,  genetics*
Animals
Base Sequence
Carrier Proteins / metabolism*
Cell Nucleus / physiology
Chromosome Deletion
Enzyme Repression / drug effects
Gene Expression Regulation, Enzymologic / drug effects*
Hela Cells
Humans
Isoenzymes / biosynthesis,  genetics*
Liver / enzymology
Mammary Tumor Virus, Mouse / genetics
Molecular Sequence Data
Oligonucleotide Probes
Plasmids
Promoter Regions, Genetic
Rats
Receptors, Retinoic Acid
Repetitive Sequences, Nucleic Acid
Thyroid Hormones / pharmacology*
Tretinoin / pharmacology*
Grant Support
ID/Acronym/Agency:
AA07261/AA/NIAAA NIH HHS; K02 AA00119/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Isoenzymes; 0/Oligonucleotide Probes; 0/Receptors, Retinoic Acid; 0/Thyroid Hormones; 302-79-4/Tretinoin; EC 1.1.1.1/Alcohol Dehydrogenase

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


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