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Cited by 118Thyroid Disorders and TreatmentsThyroid Cancer Diagnosis and TreatmentGenomics and Chromatin Dynamics

Characterization of the 5′-Flanking and 5′-Untranslated Regions of the Cyclic Adenosine 3′,5′-Monophosphate-Responsive Human Type 2 Iodothyronine Deiodinase Gene1

Bartha, Tibor, Kim, Sung-Woo, Salvatore, Domenico, Gereben, Balazs, Tu, Helen M., Harney, John W., Rudas, Peter, Larsen, P. Reed·2000·Endocrinology
DOI 10.1210/endo.141.1.7282
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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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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
DOI
10.1210/endo.141.1.7282
OpenAlex
W1996045304
Cited by
118
References
1
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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