A thyrotrope-specific variant of Pit-1 transactivates the thyrotropin beta promoter
| Autor: | Bryan R. Haugen, David F. Gordon, William M. Wood, E C Ridgway |
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| Rok vydání: | 1993 |
| Předmět: |
Gene isoform
endocrine system Messenger RNA endocrine system diseases Cell Biology Transfection Biology Biochemistry Molecular biology Transactivation medicine.anatomical_structure Anterior pituitary Cell culture Thyrotropic cell medicine Molecular Biology Transcription factor hormones hormone substitutes and hormone antagonists |
| Zdroj: | Journal of Biological Chemistry. 268:20818-20824 |
| ISSN: | 0021-9258 |
| DOI: | 10.1016/s0021-9258(19)36858-9 |
| Popis: | Thyrotropin (TSH) beta is a subunit of TSH, the expression of which is limited to the thyrotrope cells of the anterior pituitary gland. Tissue-specific expression of the mouse TSH beta gene is conferred by sequences between -270 and -80 of the 5'-flanking region. We have investigated tissue-specific expression of the TSH beta promoter in two thyrotrope-derived cell types: 1) TtT-97 thyrotropic tumors, which express the endogenous TSH beta gene, and 2) an alpha-TSH cell line, which was generated from a thyrotropic tumor that has lost the ability to express the TSH beta gene. The pituitary-specific transcription factor Pit-1 is present in thyrotropes and interacts with three cis-acting elements in the functionally important region of the TSH beta promoter. Pit-1 protein is present in TtT-97 tumor cells but is absent from alpha-TSH cells. Reintroduction of Pit-1 into alpha-TSH cells by transient transfection does not restore TSH beta promoter activity. We have identified an alternately spliced variant of Pit-1, called Pit-1T, the mRNA and protein expression of which is limited to thyrotrope-derived cells. Pit-1T contains a 14-amino acid insert in the transactivation domain due to an alternate 3' splice acceptor site. Transiently transfected Pit-1T increases TSH beta promoter activity in TtT-97 thyrotropic tumor cells, whereas additional Pit-1 has no effect. The alpha-TSH cell line, which lacks all Pit-1 proteins, requires both isoforms in order to stimulate TSH beta promoter activity. These data suggest that Pit-1T is a thyrotrope-specific splice variant of Pit-1 that is required for TSH beta promoter stimulation; furthermore, both Pit-1 and Pit-1T are required for TSH beta promoter activity in thyrotrope cells. |
| Databáze: | OpenAIRE |
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