Human progesterone receptor A form is a cell- and promoter-specific repressor of human progesterone receptor B function
| Autor: | Donald P. McDonnell, Manouchehr M. Shahbaz, Mark E. Goldman, Elisabetta Vegeto, D. X. Wen, Bert W. O'Malley |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Progesterone receptor B
Carcinoma Hepatocellular Progesterone receptor A Transcription Genetic Blotting Western Repressor Progesterone Receptor Isoform A macromolecular substances Biology Kidney Transfection Calcitriol receptor Cell Line Receptors Glucocorticoid Endocrinology Progesterone receptor Tumor Cells Cultured Animals Humans Luciferases Promoter Regions Genetic Molecular Biology Progesterone Genetics Liver Neoplasms Promoter DNA Haplorhini General Medicine Cell biology carbohydrates (lipids) Receptors Mineralocorticoid Gene Expression Regulation Mammary Tumor Virus Mouse Nuclear receptor Receptors Androgen bacteria Receptors Progesterone HeLa Cells |
| Zdroj: | Molecular Endocrinology. 7:1244-1255 |
| ISSN: | 1944-9917 0888-8809 |
| Popis: | Two distinct isoforms of the human progesterone receptor (hPR-A and hPR-B) have been identified previously. They differ only in that hPR-B contains an additional 164 amino acids at the amino terminus. Among various species these two forms arise as a result of either alternate initiation of translation from the same mRNA or by transcription from alternate promoters within the same gene. In order to understand the reason for their existence, we studied the transcriptional capacity of these individual receptors and observed that their activity was influenced strongly by cell and promoter context. More surprising was the observation that in promoter and cell contexts where hPR-A was inactive, it acted as a potent trans-dominant repressor of hPR-B-mediated transcription. This event occurred at substoichiometric concentrations of hPR-A and was hormone dependent. Human PR-A was not a general repressor of ligand-mediated transcription, as it had no effect on vitamin D receptor function. Interestingly, hPR-A but not hPR-B was capable of a similar inhibition of glucocorticoid, androgen, and mineralocorticoid receptor-mediated gene transcription. This suggests a specific role for the hPR-A isoform in this regulatory process. The trans-dominant effects of hPR-A were induced also by the antiprogestins ZK112993 and ZK98299 and a DNA binding defective hPR-A mutant, suggesting that the inhibitory function of hPR-A does not require DNA binding. The dual role of hPR-A as an activator or repressor of transcription defines a potential mechanism by which cells can generate dissimilar responses to a single hormone and provides a molecular explanation for the existence of two distinct forms of the hPR. |
| Databáze: | OpenAIRE |
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