Deubiquitination of type 2 iodothyronine deiodinase by von Hippel-Lindau protein-interacting deubiquitinating enzymes regulates thyroid hormone activation

Cyntia Curcio-Morelli, Ann Marie Zavacki, Marcelo Christofollete, Balazs Gereben, Beatriz C G De Freitas, John W. Harney, Zaibo Li, Guan Wu, Antonio C. Bianco

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

The type 2 iodothyronine deiodinase (D2) is an integral membrane ER-resident selenoenzyme that activates the pro-hormone thyroxine (T4) and supplies most of the 3,5,3′-triiodothyronine (T3) that is essential for brain development. D2 is inactivated by selective conjugation to ubiquitin, a process accelerated by T4 catalysis and essential for the maintenance of T3 homeostasis. A yeast two-hybrid screen of a human-brain library with D2 as bait identified von Hippel-Lindau protein-interacting deubiquitinating enzyme-1 (VDU1). D2 interaction with VDU1 and VDU2, a closely related deubiquitinase, was confirmed in mammalian cells. Both VDU proteins colocalize with D2 in the ER, and their coexpression prolongs D2 half-life and activity by D2 deubiquitination. VDU1, but not VDU2, is markedly increased in brown adipocytes by norepinephrine or cold exposure, further amplifying the increase in D2 activity that results from catecholamine-stimulated de novo synthesis. Thus, deubiquitination regulates the supply of active thyroid hormone to brown adipocytes and other D2-expressing cells.

Original languageEnglish
Pages (from-to)189-196
Number of pages8
JournalJournal of Clinical Investigation
Volume112
Issue number2
DOIs
StatePublished - Jul 1 2003

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Brown Adipocytes
Iodide Peroxidase
Thyroid Hormones
Brain
Triiodothyronine
Ubiquitin
Catalysis
Thyroxine
Catecholamines
Half-Life
Norepinephrine
Proteins
Homeostasis
Yeasts
Maintenance
Hormones
Membranes
Deubiquitinating Enzymes
iodothyronine deiodinase type II

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Curcio-Morelli, C., Zavacki, A. M., Christofollete, M., Gereben, B., De Freitas, B. C. G., Harney, J. W., ... Bianco, A. C. (2003). Deubiquitination of type 2 iodothyronine deiodinase by von Hippel-Lindau protein-interacting deubiquitinating enzymes regulates thyroid hormone activation. Journal of Clinical Investigation, 112(2), 189-196. https://doi.org/10.1172/JCI200318348

Deubiquitination of type 2 iodothyronine deiodinase by von Hippel-Lindau protein-interacting deubiquitinating enzymes regulates thyroid hormone activation. / Curcio-Morelli, Cyntia; Zavacki, Ann Marie; Christofollete, Marcelo; Gereben, Balazs; De Freitas, Beatriz C G; Harney, John W.; Li, Zaibo; Wu, Guan; Bianco, Antonio C.

In: Journal of Clinical Investigation, Vol. 112, No. 2, 01.07.2003, p. 189-196.

Research output: Contribution to journalArticle

Curcio-Morelli, C, Zavacki, AM, Christofollete, M, Gereben, B, De Freitas, BCG, Harney, JW, Li, Z, Wu, G & Bianco, AC 2003, 'Deubiquitination of type 2 iodothyronine deiodinase by von Hippel-Lindau protein-interacting deubiquitinating enzymes regulates thyroid hormone activation', Journal of Clinical Investigation, vol. 112, no. 2, pp. 189-196. https://doi.org/10.1172/JCI200318348
Curcio-Morelli, Cyntia ; Zavacki, Ann Marie ; Christofollete, Marcelo ; Gereben, Balazs ; De Freitas, Beatriz C G ; Harney, John W. ; Li, Zaibo ; Wu, Guan ; Bianco, Antonio C. / Deubiquitination of type 2 iodothyronine deiodinase by von Hippel-Lindau protein-interacting deubiquitinating enzymes regulates thyroid hormone activation. In: Journal of Clinical Investigation. 2003 ; Vol. 112, No. 2. pp. 189-196.
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