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Gene Review

Tg  -  thyroglobulin

Rattus norvegicus

Synonyms: Thyroglobulin
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Disease relevance of Tg


Psychiatry related information on Tg

  • Autoantibodies to Tg were produced in about one-half of anti-Id immunized mice, whereas Id' was detected in all but one mouse [6].

High impact information on Tg


Chemical compound and disease context of Tg


Biological context of Tg


Anatomical context of Tg

  • Formation of disulfide-linked Tg adducts with endoplasmic reticulum (ER) oxidoreductases begins cotranslationally [17].
  • Furthermore, chromatin immunoprecipitation experiments in FRTL-5 cells confirmed that Tg is a bona fide target gene for DREAM transrepression in thyroid follicular cells [14].
  • Tg transcytosis is a novel function of megalin, which usually transports ligands to lysosomes [1].
  • To investigate whether Tg release resulted from transcytosis, we studied FRTL-5 cells cultured as polarized layers with tight junctions on permeable filters in the upper chamber of dual chambered devices [1].
  • 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 [18].

Associations of Tg with chemical compounds


Physical interactions of Tg

  • TTF-1 binding to the proximal region overlaps with that for a novel protein present in FRTL-5 cells which can also recognize the promoter-proximal region of Tg [21].
  • Insulin and insulin-like growth factor I regulate a thyroid-specific nuclear protein that binds to the thyroglobulin promoter [22].
  • The region of Tg involved in the binding to RHL-1 was investigated by ligand blot assays with biotinylated rCRD(RHL-1) on thermolysin-digested native and desialated rat thyroglobulin [23].

Enzymatic interactions of Tg


Regulatory relationships of Tg

  • Furthermore, the 210-kDa Tg polypeptide inhibited megalin binding to intact Tg by approximately 70% [25].
  • Both insulin and IGF-I stimulate transcription from the Tg promoter in a transient transfection assay demonstrating that the promoter used contains the DNA signals necessary for insulin and IGF-I regulation [22].
  • As one possibility, this suggested there might be a hitherto unrecognized suppressor of TTF-1 RNA levels and TSH-induced Tg synthesis in individual follicles [26].
  • Transfected into rat thyroid FRTL-5 cells, the activity of reporter plasmid containing the rat TG promoter ligated to a luciferase gene was significantly suppressed in the presence of TNF-alpha [27].
  • These results demonstrate (1) that cathepsin B expression in the thyroid is regulated in parallel with that of thyroglobulin and actin, and (2) that cyclic AMP- and Ca2+-dependent processes stimulate gene expression, while phorbol ester treatment inhibits gene expression in FRTL5 cells [28].

Other interactions of Tg

  • Mixed-disulfide folding intermediates between thyroglobulin and endoplasmic reticulum resident oxidoreductases ERp57 and protein disulfide isomerase [17].
  • The half-lives of TG, Pax8, and TTF-1 are increased in endotoxin-treated cells [15].
  • We demonstrate that the TG promoter mutated at the Pax8 or TTF-1 binding element in the C site does not respond to LPS [15].
  • In the present study, we have investigated the interactions of endogenous Tg with calreticulin and with several other ER chaperones [18].
  • In contrast to the contribution of NFI proteins to constitutive gene expression in other systems, we demonstrate that follicular TG transcriptionally represses all NFI RNAs (NFI-A, -B, -C, and -X) in association with decreased NFI binding and that the RNA levels decrease as early as 4 h after TG treatment [29].

Analytical, diagnostic and therapeutic context of Tg

  • The amount of Tg internalized (measured by ELISA in the cell lysates) was reduced by RAP and 1H2, indicating that Tg endocytosis is partially mediated by megalin [19].
  • Although TG treatment for 48 h results in a decrease in NFI protein-DNA complexes measured in DNA mobility shift assays, NFI proteins are still detectable by Western analysis [29].
  • In immunoprecipitation experiments, the Tg sequence Arg-2489-Lys-2503 (required for binding to megalin and heparan sulfate proteoglycans) was found to be more exposed in low-horm-rTg, which accounted for its preferential transcytosis [4].
  • Affinity chromatography using Tg as an affinity ligand demonstrated that ERp29 might be selectively isolated from the FRTL-5 cell lysate or purified lumenal fraction of rat liver microsomes along with the other ER chaperones [30].
  • We characterized the 210-kDa Tg polypeptide by matrix-assisted laser desorption/ionization mass spectrometry analysis and found that it corresponds to the carboxyl-terminal portion of rat Tg [25].


  1. Role of megalin (gp330) in transcytosis of thyroglobulin by thyroid cells. A novel function in the control of thyroid hormone release. Marinò, M., Zheng, G., Chiovato, L., Pinchera, A., Brown, D., Andrews, D., McCluskey, R.T. J. Biol. Chem. (2000) [Pubmed]
  2. Unfolded protein response is involved in the pathology of human congenital hypothyroid goiter and rat non-goitrous congenital hypothyroidism. Baryshev, M., Sargsyan, E., Wallin, G., Lejnieks, A., Furudate, S., Hishinuma, A., Mkrtchian, S. J. Mol. Endocrinol. (2004) [Pubmed]
  3. Lithium as adjuvant to radioiodine therapy in differentiated thyroid carcinoma: clinical and in vitro studies. Liu, Y.Y., van der Pluijm, G., Karperien, M., Stokkel, M.P., Pereira, A.M., Morreau, J., Kievit, J., Romijn, J.A., Smit, J.W. Clin. Endocrinol. (Oxf) (2006) [Pubmed]
  4. Preferential megalin-mediated transcytosis of low-hormonogenic thyroglobulin: a control mechanism for thyroid hormone release. Lisi, S., Pinchera, A., McCluskey, R.T., Willnow, T.E., Refetoff, S., Marcocci, C., Vitti, P., Menconi, F., Grasso, L., Luchetti, F., Collins, A.B., Marino, M. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  5. Extinction and activation of the thyroglobulin promoter in hybrids of differentiated and transformed thyroid cells. Bonapace, I.M., Sanchez, M., Obici, S., Gallo, A., Garofalo, S., Gentile, R., Cocozza, S., Avvedimento, E.V. Mol. Cell. Biol. (1990) [Pubmed]
  6. Induction of autoantibodies to thyroglobulin by anti-idiotypic antibodies. Zanetti, M., Rogers, J., Katz, D.H. J. Immunol. (1984) [Pubmed]
  7. Reactivation of thyroglobulin gene expression in transformed thyroid cells by 5-azacytidine. Avvedimento, E.V., Obici, S., Sanchez, M., Gallo, A., Musti, A., Gottesman, M.E. Cell (1989) [Pubmed]
  8. Cellular events in the induction of experimental allergic encephalomyelitis in rats. Ortiz-Ortiz, L., Weigle, W.O. J. Exp. Med. (1976) [Pubmed]
  9. Increased expression of tumor necrosis factor-alpha and decreased expression of thyroglobulin and thyroid peroxidase mRNA levels in the thyroids of iodide-treated BB/Wor rats. Mori, K., Mori, M., Stone, S., Braverman, L.E., DeVito, W.J. Eur. J. Endocrinol. (1998) [Pubmed]
  10. Adenoviral-mediated gene therapy for thyroid carcinoma using thymidine kinase controlled by thyroglobulin promoter demonstrates high specificity and low toxicity. Zhang, R., Straus, F.H., DeGroot, L.J. Thyroid (2001) [Pubmed]
  11. Characterization of different types of experimental autoimmune thyroiditis in the Buffalo strain rat. Cohen, S.B., Weetman, A.P. Clin. Exp. Immunol. (1987) [Pubmed]
  12. The influence of methimazole on thyroglobulin-induced autoimmune thyroiditis in the rat. Rennie, D.P., McGregor, A.M., Keast, D., Weetman, A.P., Foord, S.M., Dieguez, C., Williams, E.D., Hall, R. Endocrinology (1983) [Pubmed]
  13. Isolation of thyroglobulin messenger RNA from rats: increased yield in propylthiouracil-induced hyperplasia. Scherberg, N.H. Biochem. Biophys. Res. Commun. (1978) [Pubmed]
  14. Transcriptional repressor DREAM interacts with thyroid transcription factor-1 and regulates thyroglobulin gene expression. Rivas, M., Mellström, B., Naranjo, J.R., Santisteban, P. J. Biol. Chem. (2004) [Pubmed]
  15. Bacterial lipopolysaccharide stimulates the thyrotropin-dependent thyroglobulin gene expression at the transcriptional level by involving the transcription factors thyroid transcription factor-1 and paired box domain transcription factor 8. Vélez, M.L., Costamagna, E., Kimura, E.T., Fozzatti, L., Pellizas, C.G., Montesinos, M.M., Lucero, A.M., Coleoni, A.H., Santisteban, P., Masini-Repiso, A.M. Endocrinology (2006) [Pubmed]
  16. Autoregulation of thyroid-specific gene transcription by thyroglobulin. Suzuki, K., Lavaroni, S., Mori, A., Ohta, M., Saito, J., Pietrarelli, M., Singer, D.S., Kimura, S., Katoh, R., Kawaoi, A., Kohn, L.D. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  17. Mixed-disulfide folding intermediates between thyroglobulin and endoplasmic reticulum resident oxidoreductases ERp57 and protein disulfide isomerase. Di Jeso, B., Park, Y.N., Ulianich, L., Treglia, A.S., Urbanas, M.L., High, S., Arvan, P. Mol. Cell. Biol. (2005) [Pubmed]
  18. Folding of thyroglobulin in the calnexin/calreticulin pathway and its alteration by loss of Ca2+ from the endoplasmic reticulum. Di Jeso, B., Ulianich, L., Pacifico, F., Leonardi, A., Vito, P., Consiglio, E., Formisano, S., Arvan, P. Biochem. J. (2003) [Pubmed]
  19. Megalin (gp330) is an endocytic receptor for thyroglobulin on cultured fisher rat thyroid cells. Marinò, M., Zheng, G., McCluskey, R.T. J. Biol. Chem. (1999) [Pubmed]
  20. Megalin (gp330): a putative endocytic receptor for thyroglobulin (Tg). Zheng, G., Marino', M., Zhao, J., McCluskey, R.T. Endocrinology (1998) [Pubmed]
  21. Cell-type-specific expression of the rat thyroperoxidase promoter indicates common mechanisms for thyroid-specific gene expression. Francis-Lang, H., Price, M., Polycarpou-Schwarz, M., Di Lauro, R. Mol. Cell. Biol. (1992) [Pubmed]
  22. Insulin and insulin-like growth factor I regulate a thyroid-specific nuclear protein that binds to the thyroglobulin promoter. Santisteban, P., Acebrón, A., Polycarpou-Schwarz, M., Di Lauro, R. Mol. Endocrinol. (1992) [Pubmed]
  23. The rat asialoglycoprotein receptor binds the amino-terminal domain of thyroglobulin. Montuori, N., Pacifico, F., Mellone, S., Liguoro, D., Di Jeso, B., Formisano, S., Gentile, F., Consiglio, E. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  24. Sequential reactivity of tyrosyl residues of thyroglobulin upon iodination catalyzed by thyroid peroxidase. Gavaret, J.M., Dème, D., Nunez, J., Salvatore, G. J. Biol. Chem. (1977) [Pubmed]
  25. Identification of a heparin-binding region of rat thyroglobulin involved in megalin binding. Marinò, M., Friedlander, J.A., McCluskey, R.T., Andrews, D. J. Biol. Chem. (1999) [Pubmed]
  26. In vivo expression of thyroid transcription factor-1 RNA and its relation to thyroid function and follicular heterogeneity: identification of follicular thyroglobulin as a feedback suppressor of thyroid transcription factor-1 RNA levels and thyroglobulin synthesis. Suzuki, K., Mori, A., Lavaroni, S., Miyagi, E., Ulianich, L., Katoh, R., Kawaoi, A., Kohn, L.D. Thyroid (1999) [Pubmed]
  27. Tumor necrosis factor-alpha regulation of thyroid transcription factor-1 and Pax-8 in rat thyroid FRTL-5 cells. Ohmori, M., Harii, N., Endo, T., Onaya, T. Endocrinology (1999) [Pubmed]
  28. Thyrotrophin, forskolin and ionomycin increase cathepsin B mRNA concentrations in rat thyroid cells in culture. Phillips, I.D., Black, E.G., Sheppard, M.C., Docherty, K. J. Mol. Endocrinol. (1989) [Pubmed]
  29. Thyroglobulin repression of thyroid transcription factor 1 (TTF-1) gene expression is mediated by decreased DNA binding of nuclear factor I proteins which control constitutive TTF-1 expression. Nakazato, M., Chung, H.K., Ulianich, L., Grassadonia, A., Suzuki, K., Kohn, L.D. Mol. Cell. Biol. (2000) [Pubmed]
  30. Identification of ERp29, an endoplasmic reticulum lumenal protein, as a new member of the thyroglobulin folding complex. Sargsyan, E., Baryshev, M., Szekely, L., Sharipo, A., Mkrtchian, S. J. Biol. Chem. (2002) [Pubmed]
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