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Molecular Endocrinology Vol. 6, No. 4 572-580
doi:10.1210/me.6.4.572
Copyright © 1992 by the Endocrine Society.
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Molecular Endocrinology, Vol 6, 572-580, Copyright © 1992 by Endocrine Society


ARTICLES

Inhibition of tyrosine aminotransferase gene expression by retinoic acid

CJ Pan, LL Shelly, DS Rabin and JY Chou
Human Genetics Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.

Regulation of tyrosine aminotransferase (TAT) gene expression was examined in RALA255-10G, a simian virus-40 tsA mutant-immortalized adult rat hepatocyte line. At the nonpermissive temperature (40 C), these hepatocytes exhibited a differentiated phenotype and actively expressed the TAT gene, but only in the presence of dexamethasone (DEX). The glucocorticoid-mediated TAT expression was inhibited by cycloheximide, a protein synthesis inhibitor, and by RU486, a glucocorticoid antagonist, suggesting that glucocorticoid induction requires protein synthesis and may be mediated through hormone receptors. (Bu)2cAMP (Bt2cAMP) or retinoic acid, individually or in combination, failed to increase TAT mRNA levels. However, Bt2cAMP greatly potentiated the induction by DEX, whereas retinoic acid inhibited the induction by DEX or DEX/Bt2cAMP. Nuclear run-on assays demonstrated that the induction of TAT expression by DEX or DEX/Bt2cAMP in RALA255-10G cells is regulated primarily at the transcriptional level. In contrast, retinoic acid antagonized the DEX- or DEX/Bt2cAMP- mediated induction without affecting the rate of TAT gene transcription. Instead, retinoic acid destabilized TAT mRNA. The half- life values of TAT mRNA in DEX/Bt2cAMP- and DEX/Bt2cAMP/retinoic acid- treated cells were approximately 235-270 min and 90-100 min, respectively. Our results indicate that inhibition of TAT expression by retinoic acid was regulated primarily at the posttranscriptional level.


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E. D.E. Liaudet-Coopman and A. Wellstein
Regulation of Gene Expression of a Binding Protein for Fibroblast Growth Factors by Retinoic Acid
J. Biol. Chem., August 30, 1996; 271(35): 21303 - 21308.
[Abstract] [Full Text] [PDF]




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