ArticleThe Journal of biological chemistry2011
Maturation of thyroglobulin protein region I.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 29 citations in OpenAlex.
- Substrate for Thyroid Hormone Synthesis: Biochemistry, Evolution, and Physiology.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Thyroidal expression of ER molecular chaperone GRP170 is required for efficient TSH-mediated thyroid hormone synthesis.JCI insight · 2025Article
- Anaplastic thyroid carcinoma: vimentin segregates at the invasive front of tumors in a murine xenograft model.Histochemistry and cell biology · 2024Article
- Structural features of thyroglobulin linked to protein trafficking.Protein science : a publication of the Protein Society · 2023Article
- Increased hexosamine biosynthetic pathway flux alters cell-cell adhesion in INS-1E cells and murine islets.Endocrine · 2023Article
- Genetic Factors Causing Thyroid Dyshormonogenesis as the Major Etiologies for Primary Congenital Hypothyroidism: Clinical and Genetic Characterization of 33 Patients.Journal of clinical medicine · 2022Article
- Thyroid hormone synthesis continues despite biallelic thyroglobulin mutation with cell death.JCI insight · 2021Article
- Thyroglobulin Interactome Profiling Defines Altered Proteostasis Topology Associated With Thyroid Dyshormonogenesis.Molecular & cellular proteomics : MCP · 2021Article
- Increased Prevalence of TG and TPO Mutations in Sudanese Children With Congenital Hypothyroidism.The Journal of clinical endocrinology and metabolism · 2020Article
- The role of thyroglobulin in thyroid hormonogenesis.Nature reviews. Endocrinology · 2019Review
- Relationship between the dimerization of thyroglobulin and its ability to form triiodothyronine.The Journal of biological chemistry · 2018Article
- Thyroglobulin From Molecular and Cellular Biology to Clinical Endocrinology.Endocrine reviews · 2016Review
- Transient covalent interactions of newly synthesized thyroglobulin with oxidoreductases of the endoplasmic reticulum.The Journal of biological chemistry · 2014Article
- Molecular assembly of thyroglobulin induced by in vitro nitric oxide treatments: implication its role in thyroid cells.The protein journal · 2013Article
- Orchestration of secretory protein folding by ER chaperones.Biochimica et biophysica acta · 2013Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
In vertebrates, the thyroglobulin (Tg) gene product must be exported to the lumen of thyroid follicles for thyroid hormone synthesis. In toto, Tg is composed of multiple type-1 repeats connected by linker and hinge (altogether considered as "region I," nearly 1,200 residues); regions II-III (~720 residues); and cholinesterase-like (ChEL) domain (~570 residues). Regions II-III and ChEL rapidly acquire competence for secretion, yet regions I-II-III require 20 min to become a partially mature disulfide isomer; stabilization of a fully oxidized form requires ChEL. Transition from partially mature to mature Tg occurs as a discrete "jump" in mobility by nonreducing SDS-PAGE, suggesting formation of at most a few final pairings of Cys residues that may be separated by significant intervening primary sequence. Using two independent approaches, we have investigated which portion of Tg is engaged in this late stage of its maturation. First, we demonstrate that this event is linked to oxidation involving region I. Introduction of the Tg-C1245R mutation in the hinge (identical to that causing human goitrous hypothyroidism) inhibits this maturation, although the Cys-1245 partner remains unidentified. Second, we find that Tg truncated after its fourth type-1 repeat is a fully independent secretory protein. Together, the data indicate that final acquisition of secretory competence includes conformational maturation in the interval between linker and hinge segments of region I.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.