Pax-8 protein levels regulate thyroglobulin gene expression
Open accessAbstract
Pax proteins are transcription factors that control differentiation of several cell types. In adult organisms Pax-8 is expressed in the follicular thyroid cell where it interacts with sequences of thyroglobulin and thyroperoxidase promoters. In this study, we provide evidence indicating that Pax-8 protein levels regulate thyroglobulin gene transcription. The most critical approach consisted in increasing Pax-8 protein levels by transfecting thyroid cells with a Pax-8 expression vector. In this situation the thyroglobulin promoter transcriptional activity was significantly increased with respect to untransfected cells. In contrast, the transfection of thyroid transcription factor-1 (TTF-1) expression vector causes a modest decrease of thyroglobulin promoter activity, rather than an increase. Northern blots of human papillary cancers reveal a significant correlation between Pax-8 and thyroglobulin mRNAs. Gel-retardation assays suggest that the mechanism by which the Pax-8 protein levels modulate thyroglobulin promoter activity may occur through competition with TTF-1 for a common binding site. Since we also demonstrate that Pax-8 expression is subjected to TSH control, our data strongly suggest that Pax-8 protein levels could represent an important determinant for the regulation of thyroid cells.
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TSH can stimulate PAX8 mRNA and protein expression, likely via the CREB binding sites in the PAX8 gene promoter, as demonstrated in PCCl3 and FRTL-5 cells.
“TSH can stimulate PAX8 mRNA and protein expression, likely via the CREB binding sites in the PAX8 gene promoter, as demonstrated in PCCl3 and FRTL-5 cells (144, 153).”
From Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion (2022) · cites this paper as [153]
The Results (Fig. 1; page not specified in our copy) show that TSH increases Pax-8 protein levels in FRTL-5 cells through a cAMP-dependent mechanism. The paper does not demonstrate TSH-induced Pax-8 mRNA expression in these cells, report experiments in PCCl3 cells, or identify CREB binding sites in the PAX8 promoter as the mechanism. (LLM, conf=0.89)
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Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion
Jing, L., & Zhang, Q. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.992883 · Cited by 61 · see citing works
- Authors
- Fabbro, D., Pellizzari, L., Mercuri, F., Tell, G., & Damante, G.
- Affiliations
- University of Udine (IT)
- ORCID
- Venue
- Journal of Molecular Endocrinology
- Publisher
- Bioscientifica
- Published
- 1998-12-01
- Volume
- 21
- Issue
- 3
- Pages
- 347-354
- ISSN
- 0952-5041 (ISSN-L)
- 1479-6813
- OpenAlex
- W2132356768
- Cited by
- 69
- References
- 0
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2019: 2 · 2018: 1 · 2016: 2 · 2013: 1 · 2012: 2
- FWCI
- 2.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Molecular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System (University of Udine) (submittedVersion)
- Funders
- Consiglio Nazionale delle Ricerche
- Associazione Italiana per la Ricerca sul Cancro
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- PAX8, thyroglobulin promoter, TTF-1, transcriptional regulation, thyroid follicular cells, papillary thyroid carcinoma, transcription factor competition, thyroid differentiation
- MeSH terms
- PAX8 Transcription Factor, Thyroid Nuclear Factor 1, Base Sequence, Cell Line, DNA-Binding Proteins, Gene Expression Regulation, Humans, Nuclear Proteins, Promoter Regions, Genetic, RNA, Messenger, RNA, Neoplasm, Thyroglobulin, Thyroid Gland, Thyroid Neoplasms, Thyrotropin, Transcription Factors, Transfection, Oligonucleotide Probes, Trans-Activators, Paired Box Transcription Factors
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