ArticleThe Biochemical journal2003
Folding of thyroglobulin in the calnexin/calreticulin pathway and its alteration by loss of Ca2+ from the endoplasmic reticulum.
Article in The Biochemical journal, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 56 citations in OpenAlex.
- A PRK-armed oncolytic adenovirus drives calreticulin exposure for dendritic cell licensing to prime antitumor CD8⁺ T cells and synergizes with anti-PD-1 or CAR-T therapy in colorectal cancer.Journal of gastroenterology · 2026Article
- Article
- Endoplasmic reticulum stress in Hashimoto's thyroiditis: a candidate amplification node linking thyroid-specific vulnerability and immune dysregulation.Frontiers in immunology · 2026Review
- Public Cohort Analysis Identifies Thyroglobulin Variants as Hypothyroidism Risk Factors.bioRxiv : the preprint server for biology · 2025Article
- Thyroidal expression of ER molecular chaperone GRP170 is required for efficient TSH-mediated thyroid hormone synthesis.JCI insight · 2025Article
- Competition for calnexin binding regulates secretion and turnover of misfolded GPI-anchored proteins.The Journal of cell biology · 2023Article
- Defective Thyroglobulin: Cell Biology of Disease.International journal of molecular sciences · 2022Review
- The Role of Hsp90 in Retinal Proteostasis and Disease.Biomolecules · 2022Review
- STIM1 Deficiency In Intestinal Epithelium Attenuates Colonic Inflammation and Tumorigenesis by Reducing ER Stress of Goblet Cells.Cellular and molecular gastroenterology and hepatology · 2022Article
- Thyrocyte cell survival and adaptation to chronic endoplasmic reticulum stress due to misfolded thyroglobulin.The Journal of biological chemistry · 2020Article
- The Pervasive Effects of ER Stress on a Typical Endocrine Cell: Dedifferentiation, Mesenchymal Shift and Antioxidant Response in the Thyrocyte.Frontiers in endocrinology · 2020Article
- The role of thyroglobulin in thyroid hormonogenesis.Nature reviews. Endocrinology · 2019Review
- Recent Insights Into the Pathogenic Mechanism of Pancreatitis: Role of Acinar Cell Organelle Disorders.Pancreas · 2019Review
- Binding of thyroglobulin (Tg) to the low-density lipoprotein receptor-associated protein (RAP) during the biosynthetic pathway prevents premature Tg interactions with sortilin.Journal of endocrinological investigation · 2017Article
- Intracellular retention of thyroglobulin in the absence of the low-density lipoprotein receptor-associated protein (RAP) is likely due to premature binding to megalin in the biosynthetic pathway.Journal of endocrinological investigation · 2016Article
- Thyroglobulin From Molecular and Cellular Biology to Clinical Endocrinology.Endocrine reviews · 2016Review
- Canonical transient receptor potential channel 2 (TRPC2): old name-new games. Importance in regulating of rat thyroid cell physiology.Pflugers Archiv : European journal of physiology · 2014Review
- Transient covalent interactions of newly synthesized thyroglobulin with oxidoreductases of the endoplasmic reticulum.The Journal of biological chemistry · 2014Article
- Orchestration of secretory protein folding by ER chaperones.Biochimica et biophysica acta · 2013Review
- The Mediation of Hepatic Lipogenesis Through Estrogens.Postdoc journal : a journal of postdoctoral research and postdoctoral affairs · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
During its initial folding in the endoplasmic reticulum (ER), newly synthesized thyroglobulin (Tg) is known to interact with calnexin and other ER molecular chaperones, but its interaction with calreticulin has not been examined previously. In the present study, we have investigated the interactions of endogenous Tg with calreticulin and with several other ER chaperones. We find that, in FRTL-5 and PC-Cl3 cells, calnexin and calreticulin interact with newly synthesized Tg in a carbohydrate-dependent manner, with largely overlapping kinetics that are concomitant with the maturation of Tg intrachain disulphide bonds, preceding Tg dimerization and exit from the ER. Calreticulin co-precipitates more newly synthesized Tg than does calnexin; however, using two different experimental approaches, calnexin and calreticulin were found in ternary complexes with Tg, making this the first endogenous protein reported in ternary complexes with calnexin and calreticulin in the ER of live cells. Depletion of Ca(2+) from the ER elicited by thapsigargin (a specific inhibitor of ER Ca(2+)-ATPases) results in retention of Tg in this organelle. Interestingly, thapsigargin treatment induces the premature exit of Tg from the calnexin/calreticulin cycle, while stabilizing and prolonging interactions of Tg with BiP (immunoglobulin heavy chain binding protein) and GRP94 (glucose-regulated protein 94), two chaperones whose binding is not carbohydrate-dependent. Our results suggest that calnexin and calreticulin, acting in ternary complexes with a large glycoprotein substrate such as Tg, might be engaged in the folding of distinct domains, and indicate that lumenal Ca(2+) strongly influences the folding of exportable glycoproteins, in part by regulating the balance of substrate binding to different molecular chaperone systems within the ER.
Indexed as
Identifiers
What OpenQuestion holds
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.