Selective Proteolysis of Human Type 2 Deiodinase: A Novel Ubiquitin-Proteasomal Mediated Mechanism for Regulation of Hormone Activation
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We investigated the mechanism by which T4 regulates its activation to T3 by the type 2 iodothyronine deiodinase (D2). D2 is a short- lived (t1/2 50 min), 31-kDa endoplasmic reticulum (ER) integral membrane selenoenzyme that generates intracellular T3. Inhibition of the ubiquitin (Ub) activating enzyme, E1, or MG132, a proteasome blocker, inhibits both the basal and substrate-induced acceleration of D2 degradation. Using a catalytically active transiently expressed FLAG-tagged-NH2-D2, we found rapid synthesis of high molecular mass (100-300 kDa) Ub-D2 conjugates that are catalytically inactive. Ub-D2 increases when cells are exposed to D2 substrate or MG132 and disappears rapidly after E1 inactivation. Fusion of FLAG epitope to the COOH terminus of D2 prolongs its half-life approximately 2.5-fold and increases the levels of active and, especially, Ub-D2. This indicates that COOH-terminal modification interferes with proteasomal uptake of Ub-D2 that can then be deubiquitinated. Interestingly, the type 1 deiodinase, a related selenoenzyme that also converts T4 to T3 but with a half-life of >12 h, is inactivated but not ubiquitinated or degraded after exposure to substrate. Thus, ubiquitination of the ER-resident enzyme D2 constitutes a specific posttranslational mechanism for T4 regulation of its own activation in the central nervous system and pituitary tissues in which D2-catalyzed T4 to T3 conversion is the major source of intracellular T3.
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T4 induces ubiquitination and proteasomal degradation of D2, limiting T3 production via this pathway.
“T4 induces ubiquitination and proteasomal degradation of D2, limiting T3 production via this pathway (45).”
From Treatment Preferences in Patients With Hypothyroidism (2025) · cites this paper as [45]
T4 and rT3 inhibit DIO2 by promoting its ubiquitination, which inhibits DIO2 activity and targets it for proteasomal degradation, forming an incoherent feedforward motif with T3 as the output.
“T4 and rT3 also inhibit DIO2 by promoting its ubiquitination, which inhibits DIO2 activity and targets it for proteasomal degradation (37–40), forming an incoherent feedforward motif with T3 as the output.”
From Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion (2022) · cites this paper as [38]
D2 protein levels and activity are regulated by post-translational mechanisms, especially ubiquitination, which appears to be induced mainly by T4.
“It has been shown that D2 protein levels and activity are regulated by post-translational mechanisms, especially ubiquitination (Gereben et al. 2000), which appears to be induced mainly by T4.”
From Administration of 3,5-diiodothyronine (3,5-T2) causes central hypothyroidism and stimulates thyroid-sensitive tissues (2014) · cites this paper as Gereben et al. 2000
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Cites
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302 · see citing works
Hershko, A., & Ciechanover, A. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.425 · Cited by 8,840 · see citing works
Tight control of gene expression in mammalian cells by tetracycline-responsive promoters.
Gossen, M., & Bujard, H. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.12.5547 · Cited by 4,943 · cited 1× · see citing works
“All constructs were cloned into the D10 mammalian expression vector (23).”
Salceda, S., & Caro, J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.36.22642 · Cited by 1,674 · see citing works
Regulated Intramembrane Proteolysis
Brown, M. S., Ye, J., Rawson, R. B., & Goldstein, J. L. (2000) · Cell · doi:10.1016/s0092-8674(00)80675-3 · Cited by 1,329 · see citing works
UBIQUITIN AND THE CONTROL OF PROTEIN FATE IN THE SECRETORY AND ENDOCYTIC PATHWAYS
Bonifacino, J. S., & Weissman, A. M. (1998) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.14.1.19 · Cited by 607 · see citing works
Larsen, P. R., Silva, J. E., & Kaplan, M. M. (1981) · Endocrine Reviews · doi:10.1210/edrv-2-1-87 · Cited by 546 · see citing works
Self-citationMolecular biological and biochemical characterization of the human type 2 selenodeiodinase.
Salvatore, D., Bartha, T., Harney, J. W., & Larsen, P. R. (1996) · Endocrinology · doi:10.1210/endo.137.8.8754756 · Cited by 284 · see citing works
Self-citationAccumulation of p53 in a Mutant Cell Line Defective in the Ubiquitin Pathway
Chowdary, D., Dermody, J. J., Jha, K. K., & Ozer, H. L. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.3.1997 · Cited by 278 · see citing works
Cerebral cortex responds rapidly to thyroid hormones
Leonard, J. L., Kaplan, M. M., Visser, T. J., Silva, J. E., & Larsen, P. R. (1981) · Science · doi:10.1126/science.7291997 · Cited by 206 · see citing works
Self-citationRole of the proteasome in membrane extraction of a short‐lived ER‐transmembrane protein
Mayer, T. U., Braun, T., & Jentsch, S. (1998) · The EMBO Journal · doi:10.1093/emboj/17.12.3251 · Cited by 205 · see citing works
Silva, J. E., & Leonard, J. L. (1985) · Endocrinology · doi:10.1210/endo-116-4-1627 · Cited by 157 · see citing works
Berry, M. J. (1992) · Endocrinology · doi:10.1210/en.131.4.1848 · Cited by 114 · see citing works
Catabolite Inactivation of Fructose-1,6-bisphosphatase of Saccharomyces cerevisiae
Schork, S. M., Thumm, M., & Wolf, D. H. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.44.26446 · Cited by 113 · see citing works
Hämmerle, M., Bauer, J., Rose, M., Szallies, A., Thumm, M., Düsterhus, S., Mecke, D., Entian, K., & Wolf, D. H. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.39.25000 · Cited by 110 · see citing works
Steinsapir, J., Bianco, A. C., Buettner, C., Harney, J., & Larsen, P. R. (2000) · Endocrinology · doi:10.1210/endo.141.3.7355 · Cited by 109 · see citing works
Self-citationMcGee, T. P., Cheng, H. H., Kumagai, H., Ōmura, S., & Simoni, R. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.41.25630 · Cited by 103 · see citing works
Type 2 iodothyronine deiodinase in rat pituitary tumor cells is inactivated in proteasomes
Steinsapir, J., Harney, J., & Larsen, P. R. (1998) · Journal of Clinical Investigation · doi:10.1172/jci4672 · Cited by 102 · see citing works
Self-citationBerry, M. J., Maia, A. L., Kieffer, J. D., Harney, J. W., & Larsen, P. R. (1992) · Endocrinology · doi:10.1210/endo.131.4.1396330 · Cited by 99 · see citing works
Self-citationDegradation of Ornithine Decarboxylase by the 26S Proteasome
Murakami, Y., Matsufuji, S., Hayashi, S., Tanahashi, N., & Tanaka, K. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.1706 · Cited by 96 · see citing works
ST. GERMAIN, D. L. (1988) · Endocrinology · doi:10.1210/endo-122-5-1860 · Cited by 81 · see citing works
Germain, D. L. S. (1988) · Journal of Clinical Investigation · doi:10.1172/jci113479 · Cited by 48 · see citing works
Salvatore, D., Harney, J. W., & Larsen, P. R. (1999) · Biochimie · doi:10.1016/s0300-9084(99)80106-0 · Cited by 42 · see citing works
Self-citationGermain, D. L. S. (1986) · Endocrinology · doi:10.1210/endo-119-2-840 · Cited by 40 · see citing works
Comparison of Kidney and Brown Adipose Tissue Iodothyronine 5′-Deiodinases*
Silva, J. E., MELLEN, S. A., & Larsen, P. R. (1987) · Endocrinology · doi:10.1210/endo-121-2-650 · Cited by 29 · see citing works
Self-citationGermain, D. L. S., & Croteau, W. (1989) · Endocrinology · doi:10.1210/endo-125-5-2735 · Cited by 22 · see citing works
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Jonklaas, J., Bianco, A. C., Bauer, A. J., Burman, K. D., Cappola, A. R., Celi, F. S., Cooper, D. S., Kim, B. W., Peeters, R. P., Rosenthal, M. S., et al. (2014) · Thyroid® · doi:10.1089/thy.2014.0028 · Cited by 1,928 · see citing works
Self-citationBianco, 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 · see citing works
Self-citationCellular 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 · see citing works
Self-citationDeiodinases: implications of the local control of thyroid hormone action
Bianco, A. C., & Kim, B. W. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29812 · Cited by 845 · see citing works
Self-citationThe human selenoproteome: recent insights into functions and regulation
Reeves, M. A., & Hoffmann, P. R. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-0032-4 · Cited by 531 · see citing works
Type 2 iodothyronine deiodinase is the major source of plasma T3 in euthyroid humans
Luiza Maia, A. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25083 · Cited by 360 · see citing works
Panicker, V., Saravanan, P., Vaidya, B., Evans, J., Hattersley, A. T., Frayling, T. M., & Dayan, C. M. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-1301 · Cited by 327 · see citing works
Paradigms of dynamic control of thyroid hormone signaling
Bianco, A. C., Dumitrescu, A., Gereben, B., Ribeiro, M. O., Fonseca, T. L., Fernandes, G. W., & Bocco, B. M. L. C. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00275 · Cited by 293 · see citing works
Self-citationMelatonin feedback on clock genes: a theory involving the proteasome
Vriend, J. P., & Reiter, R. J. (2014) · Journal of Pineal Research · doi:10.1111/jpi.12189 · Cited by 268 · see citing works
Dentice, M., Bandyopadhyay, A., Gereben, B., Callebaut, I., Christoffolete, M. A., Kim, B. W., Nissim, S., Mornon, J.-P., Zavacki, A. M., Zeöld, A., et al. (2005) · Nature Cell Biology · doi:10.1038/ncb1272 · Cited by 227 · see citing works
Self-citationType 1 iodothyronine deiodinase in human physiology and disease
Maia, A. L., Goemann, I. M., Meyer, E. L. D. S., & Wajner, S. M. (2011) · Journal of Endocrinology · doi:10.1530/joe-10-0481 · Cited by 220 · see citing works
Köhrle, J. (2002) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(02)47014-0 · Cited by 208 · see citing works
Gereben, B., Zeöld, A., Dentice, M., Salvatore, D., & Bianco, A. C. (2008) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-007-7396-0 · Cited by 207 · see citing works
Self-citationBianco, A. C., Anderson, G., Forrest, D., Galton, V. A., Gereben, B., Kim, B. W., Kopp, P. A., Liao, X. H., Obregon, M. J., Peeters, R. P., et al. (2014) · Thyroid · doi:10.1089/thy.2013.0109 · Cited by 205 · see citing works
Self-citationThe classic pathways of thyroid hormone metabolism
van der Spek, A. H., Fliers, E., & Boelen, A. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.01.025 · Cited by 194 · see citing works
The molecular basis of the non-thyroidal illness syndrome
de Vries, E. M., Fliers, E., & Boelen, A. (2015) · Journal of Endocrinology · doi:10.1530/joe-15-0133 · Cited by 192 · see citing works
Werneck de Castro, J. P., Fonseca, T. L., Ueta, C. B., McAninch, E. A., Abdalla, S., Wittmann, G., Lechan, R. M., Gereben, B., & Bianco, A. C. (2015) · Journal of Clinical Investigation · doi:10.1172/jci77588 · Cited by 184 · see citing works
Self-citationvan der Ven, L. T. M., van de Kuil, T., Verhoef, A. J., Verwer, C. M., Lilienthal, H., Leonards, P. E. G., Schauer, U. M. D., Cantón, R. F., Litens, S., de Jong, F. H., et al. (2007) · Toxicology · doi:10.1016/j.tox.2007.12.009 · Cited by 179 · see citing works
Wajner, S. M., Goemann, I. M., Bueno, A. L., Larsen, P. R., & Maia, A. L. (2011) · Journal of Clinical Investigation · doi:10.1172/jci44678 · Cited by 168 · see citing works
Self-citationRole of the type 2 iodothyronine deiodinase (D2) in the control of thyroid hormone signaling
Drigo, R. A. E., Fonseca, T. L., Werneck‐de‐Castro, J. P., & Bianco, A. C. (2012) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2012.08.019 · Cited by 146 · see citing works
Self-citationda‐Silva, W. S., Harney, J. W., Kim, B. W., Li, J., Bianco, S. D. C., Crescenzi, A., Christoffolete, M. A., Huang, S. A., & Bianco, A. C. (2007) · Diabetes · doi:10.2337/db06-1488 · Cited by 148 · see citing works
Self-citationDeiodinases and the Three Types of Thyroid Hormone Deiodination Reactions
Sabatino, L., Vassalle, C., Seppia, C. D., & Iervasi, G. (2021) · Endocrinology and Metabolism · doi:10.3803/enm.2021.1198 · Cited by 149 · see citing works
Defending plasma T3 is a biological priority
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Self-citationScope and limitations of iodothyronine deiodinases in hypothyroidism
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Self-citationImpact of Oatp1c1 deficiency on thyroid hormone metabolism and action in the mouse brain
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Bianco, A. C., & Larsen, P. R. (2005) · Thyroid · doi:10.1089/thy.2005.15.777 · Cited by 137 · see citing works
Self-citationLocal control of thyroid hormone action: role of type 2 deiodinase
Williams, G. R., & Bassett, J. H. D. (2011) · Journal of Endocrinology · doi:10.1530/joe-10-0448 · Cited by 134 · see citing works
Deiodinases control local cellular and systemic thyroid hormone availability
Köhrle, J., & Frädrich, C. (2022) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2022.09.024 · Cited by 133 · see citing works
Baqui, M. M. A., Botero, D., Gereben, B., Curcio, C., Harney, J. W., Salvatore, D., Sorimachi, K., Larsen, P. R., & Bianco, A. C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210266200 · Cited by 133 · see citing works
Self-citationCurcio‐Morelli, C., Zavacki, A. M., Christoffolete, M. A., Gereben, B., Freitas, B. C. G., Harney, J. W., Li, Z., Wu, G., & Bianco, A. C. (2003) · Journal of Clinical Investigation · doi:10.1172/jci18348 · Cited by 133 · see citing works
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Préau, L., Fini, J., Morvan-Dubois, G., & DEMENEIX, B. A. (2014) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2014.06.015 · Cited by 116 · see citing works
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Friedrichsen, S., Christ, S., Heuer, H., Schäfer, M. K.-H., Mansouri, A., Bauer, K., & Visser, T. J. (2003) · Endocrinology · doi:10.1210/en.2002-220715 · Cited by 113 · see citing works
Yasuo, S., Nakao, N., Ohkura, S., Iigo, M., Hagiwara, S., Goto, A., Andō, H., Yamamura, T., Watanabe, M., Watanabe, T., et al. (2005) · Endocrinology · doi:10.1210/en.2005-0507 · Cited by 106 · see citing works
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Self-citationSagar, G. D. V., Gereben, B., Callebaut, I., Mornon, J.-P., Zeöld, A., da Silva, W. S., Luongo, C., Dentice, M., Tente, S. M., Freitas, B. C. G., et al. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00283-07 · Cited by 103 · see citing works
Self-citationThe Deiodinase Trio and Thyroid Hormone Signaling
Bianco, A. C., & da Conceição, R. R. (2018) · Methods in Molecular Biology · doi:10.1007/978-1-4939-7902-8_8 · Cited by 96 · see citing works
Self-citationMinireview: Cracking the Metabolic Code for Thyroid Hormone Signaling
Bianco, A. C. (2011) · Endocrinology · doi:10.1210/en.2011-1104 · Cited by 96 · see citing works
Self-citationCurcio, C., Baqui, M. M. A., Salvatore, D., Rihn, B. H., Mohr, S., Harney, J. W., Larsen, P. R., & Bianco, A. C. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.c100325200 · Cited by 96 · see citing works
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Kanou, Y., Hishinuma, A., Tsunekawa, K., Seki, K., Mizuno, Y., Fujisawa, H., Imai, T., Miura, Y., Nagasaka, T., Yamada, C., et al. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-1242 · Cited by 61 · see citing works
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Faunes, F., Gundermann, D. G., Muñoz, R., Bruno, R., & Larraı́n, J. (2017) · Developmental Biology · doi:10.1016/j.ydbio.2017.03.026 · Cited by 24 · see citing works
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Self-citationNappi, A., Cicco, E. D., Miro, C., Cicatiello, A. G., Sagliocchi, S., Mancino, G., Ambrosio, R., Luongo, C., Girolamo, D. D., Stefano, M. A. D., et al. (2020) · Cancers · doi:10.3390/cancers12030715 · Cited by 23 · see citing works
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Bayse, C. A., Marsan, E. S., Garcia, J. R., & Tran-Thompson, A. T. (2020) · Scientific Reports · doi:10.1038/s41598-020-72243-9 · Cited by 24 · see citing works
Sagliocchi, S., Murolo, M., Cicatiello, A. G., Miro, C., Nappi, A., Cicco, E. D., Torabinejad, S., Civita, E. L., Romano, V., Terracciano, D., et al. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106685 · Cited by 21 · see citing works
Leiria, L. B., Dora, J. M., Wajner, S. M., Estivalet, A. A. F., Crispim, D., & Maia, A. L. (2014) · PLoS ONE · doi:10.1371/journal.pone.0103960 · Cited by 21 · see citing works
Tagami, T. (2021) · Endocrine Journal · doi:10.1507/endocrj.ej21-0059 · Cited by 20 · see citing works
Sabatino, L., Lubrano, V., Balzan, S., Kusmic, C., Turco, S. D., & Iervasi, G. (2014) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-014-2235-8 · Cited by 19 · see citing works
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Hedgehog-mediated regulation of thyroid hormone action through iodothyronine deiodinases
Dentice, M. (2011) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2011.553607 · Cited by 19 · see citing works
Bagga, A. D., Johnson, B. P., & Zhang, Q. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1168663 · Cited by 18 · see citing works
- Authors
- Gereben, B., Goncalves, C., Harney, J. W., Larsen, P. R., & Bianco, A. C.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Bianco, Antonio C.
- Venue
- Molecular Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2000-11
- Volume
- 14
- Issue
- 11
- Pages
- 1697-1708
- ISSN
- 0888-8809 (ISSN-L)
- 1944-9917
- OpenAlex
- W2055205764
- Cited by
- 161
- References
- 26
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 7 · 2023: 7 · 2022: 5 · 2021: 5 · 2020: 3 · 2019: 6 · 2018: 4 · 2017: 6 · 2016: 6 · 2015: 6 · 2014: 11 · 2013: 6 · 2012: 7
- FWCI
- 3.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Universidade de São Paulo
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK036256, R01-DK-36256)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- type 2 deiodinase, selective proteolysis, ubiquitin-proteasome system, T4 to T3 conversion, selenoenzymes, endoplasmic reticulum, ubiquitination, deubiquitination, protein degradation, type I deiodinase
- MeSH terms
- Iodothyronine Deiodinase Type II, Animals, Epitopes, Base Sequence, Cell Line, Cysteine Endopeptidases, Endoplasmic Reticulum, Hormones, Humans, Iodide Peroxidase, Ligases, Molecular Sequence Data, Multienzyme Complexes, Oligopeptides, Peptides, Protein Processing, Post-Translational, Recombinant Proteins, Thyroxine, Triiodothyronine, Ubiquitins, Ubiquitin-Protein Ligases, Proteasome Endopeptidase Complex
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