The DOI matches its Crossref record; 31 of the 32 references it cites were found in a registry or an index.
Characterization of the 5′-Flanking and 5′-Untranslated Regions of the Cyclic Adenosine 3′,5′-Monophosphate-Responsive Human Type 2 Iodothyronine Deiodinase Gene1
Abstract
The type 2 iodothyronine deiodinase (D2) catalyzes T4 activation. In humans, unlike rodents, it is widely expressed, and its action probably contributes to both intracellular and plasma T3 pools. We have isolated the 6.5-kb 5'-flanking region (FR) and the previously uncloned 553 nucleotides (nt) of the 5'-untranslated region (UTR) of hdio2. The 5'-UTR is complex, with three transcription start sites (TSS) (708, 31, and approximately 24 nt 5' to the ATG), an alternatively spliced approximately 300-nt intron in the 5'-UTR, and three short open reading frames 5' to the initiator ATG. The previously reported approximately 7.5-kb D2 messenger RNA (mRNA) is actually an approximately 7-kb doublet that is present in thyroid, pituitary, cardiac and skeletal muscle, and possibly brain, but with only the longer transcript in placenta. A canonical cAMP response element-binding protein-binding site is present at about 90 bp 5' to the most 5'-TSS. It accounts for the robust response of the 6.8-kb hdio2 5'-FR to protein kinase A. Forskolin increases D2 mRNA in human thyroid cells, which may explain the high D2 mRNA in Graves' thyroid and thyroid adenomas. The hdio2 gene structure and Northern blot results suggest that D2 expression is tightly controlled and tissue specific.
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“The promoter of the DIO2 gene contains both CREB-binding site and TTF1 binding site, and TSH and TTF1 were shown to upregulate DIO2 activity ( Figure 3F ) (176, 177).”
From Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion (2022) · cites this paper as [176]
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Cited by
Bianco, A. C., Salvatore, D., Gereben, B., Berry, M. J., & Larsen, P. R. (2002) · Endocrine Reviews · doi:10.1210/edrv.23.1.0455 · Cited by 1,853
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Cellular and Molecular Basis of Deiodinase-Regulated Thyroid Hormone Signaling1
Gereben, B., Zavacki, A. M., Ribich, S., Kim, B. W., Huang, S. A., Simonides, W. S., Zeöld, A., & Bianco, A. C. (2008) · Endocrine Reviews · doi:10.1210/er.2008-0019 · Cited by 891
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Metadata
- Authors
- Bartha, T., Kim, S.-W., Salvatore, D., Gereben, B., Tu, H. M., Harney, J. W., Rudas, P., & Larsen, P. R.
- Affiliations
- the Department of Physiology and Biochemistry, University of Veterinary Science (T.B., P.R.), H-1400 Budapest, Hungary
- Brigham and Women's Hospital (US)
- University of Naples Federico II (IT)
- Thyroid Division, Department of Medicine, Brigham and Women’s Hospital Harvard Medical School (S.-W.K., B.G., H.M.T., J.W.H., P.R.L.), Boston, Massachusetts 02115
- Corresponding author
- Larsen, P. Reed
- ORCID
- Salvatore, Domenico
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2000-01-01
- Volume
- 141
- Issue
- 1
- Pages
- 229-237
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W1996045304
- Cited by
- 118
- References
- 32
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 1 · 2019: 1 · 2018: 3 · 2017: 1 · 2016: 5 · 2015: 2 · 2014: 2 · 2013: 2 · 2012: 6
- FWCI
- 6.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK36256, R01DK036256, T32DK007529, DK-07529)
- 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 › Genomics and Chromatin Dynamics
- Keywords
- type 2 deiodinase, 5'-flanking region, 5' untranslated region, transcription start sites, alternative splicing, open reading frames, CREB, protein kinase A, forskolin, triiodothyronine, thyroid cells, Graves' disease, gene expression regulation, tissue-specific gene expression
- MeSH terms
- Iodothyronine Deiodinase Type II, Adenoma, Cyclic AMP, Base Sequence, Colforsin, Humans, Introns, Iodide Peroxidase, Molecular Sequence Data, Endopeptidases, Promoter Regions, Genetic, RNA, Messenger, Thyroid Neoplasms, Thyrotropin, Transcription, Genetic, Tumor Cells, Cultured, Chloramphenicol O-Acetyltransferase, TATA Box, DNA Primers, Codon, Initiator, 5' Untranslated Regions, Exopeptidases
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- CoChat. (2026). Citation check: Characterization of the 5′-Flanking and 5′-Untranslated Regions of the Cyclic Adenosine 3′,5′-Monophosphate-Responsive Human Type 2 Iodothyronine Deiodinase Gene1. https://app.cochat.ai/papers/10.1210/endo.141.1.7282
- The paper
- Bartha, T., Kim, S.-W., Salvatore, D., Gereben, B., Tu, H. M., Harney, J. W., Rudas, P., & Larsen, P. R. (2000). Characterization of the 5′-Flanking and 5′-Untranslated Regions of the Cyclic Adenosine 3′,5′-Monophosphate-Responsive Human Type 2 Iodothyronine Deiodinase Gene1. Endocrinology. https://doi.org/10.1210/endo.141.1.7282
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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