The thyroid hormone response element is required for activation of the growth hormone gene promoter by nicotinamide analogs.
N'-Methylnicotinamide and nicotinamide, which decreased in vitro ADP-ribosylation of nuclear proteins and/or cellular NAD+ content, selectively increased the basal expression of the rat growth hormone (GH) gene promoter and its response to triiodothyronine (T3). This increase was not found when the thyroid hormone response element (TRE) was deleted from the promoter. Transfection with an expression vector for the T3 receptor inhibited basal activity of the TRE-containing promoter and repressed the stimulatory effect of N'-methylnicotinamide. The addition of hormone relieved this inhibition and enhanced transcription above levels found in the absence of the transfected receptors. These results suggest a modulatory role of ADP-ribosylation in hormonal regulation of gene expression.
Sánchez-Pacheco
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Instituto de Investigaciones Biomédicas, CSIC, Madrid, Spain.
Aranda
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D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D013006:Growth Hormone / Q000235:genetics*; D009243:NAD / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D014284:Triiodothyronine / Q000494:pharmacology*
D011988:Receptors, Thyroid Hormone; D011994:Recombinant Proteins; D014284:Triiodothyronine; D009243:NAD; D000246:Adenosine Diphosphate Ribose; D009536:Niacinamide; D013006:Growth Hormone; D015500:Chloramphenicol O-Acetyltransferase; C024058:N(1)-methylnicotinamide