The Human Type 2 Iodothyronine Deiodinase Is a Selenoprotein Highly Expressed in a Mesothelioma Cell Line

Cyntia Curcio, Munira M.A. Baqui, Domenico Salvatore, Bertrand H. Rihn, Steve Mohr, John W. Harney, P. Reed Larsen, Antonio C. Bianco

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

Types 1 and 3 iodothyronine deiodinases are known to be selenocysteine-containing enzymes. Although a putative human type 2 iodothyronine deiodinase (D2) gene (hDio2) encoding a similar selenoprotein has been identified, basal D2 activity is not selenium (Se)-dependent nor has D2 been labeled with 75Se. A human mesothelioma cell line (MSTO-211H) has recently been shown to have ∼40-fold higher levels of hDio2 mRNA than mesothelial cells. Mesothelioma cell lysates activate thyroxine (T4) to 3,5,3′-triiodothyronine with typical characteristics of D2 such as low Km (T4), 1.3 nM, resistance to propylthiouracil, and a short half-life (∼30 min). D2 activity is ∼30-fold higher in Se-supplemented than in Se-depleted medium. An antiserum prepared against a peptide deduced from the Dio2 mRNA sequence precipitates a 75Se protein of the predicted 31-kDa size from 75Se-labeled mesothelioma cells. Bromoadenosine 3′5′ cyclic monophosphate increases D2 activity and 75Se-p31 ∼2.5-fold whereas substrate (T 4) reduces both D2 activity and 75Se-p31 ∼2-3-fold. MG132 or lactacystin (10 μM), inhibitors of the proteasome pathway by which D2 is degraded, increase both D2 activity and 75Se-p31 3-4-fold and prevent the loss of D2 activity during cycloheximide or substrate (T 4) exposure. Immunocytochemical studies with affinity-purified anti-hD2 antibody show a Se-dependent increase in immunofluorescence. Thus, human D2 is encoded by hDio2 and is a member of the selenodeiodinase family accounting for its highly catalytic efficiency in T4 activation.

Original languageEnglish (US)
Pages (from-to)30183-30187
Number of pages5
JournalJournal of Biological Chemistry
Volume276
Issue number32
DOIs
StatePublished - Aug 10 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Curcio, C., Baqui, M. M. A., Salvatore, D., Rihn, B. H., Mohr, S., Harney, J. W., Larsen, P. R., & Bianco, A. C. (2001). The Human Type 2 Iodothyronine Deiodinase Is a Selenoprotein Highly Expressed in a Mesothelioma Cell Line. Journal of Biological Chemistry, 276(32), 30183-30187. https://doi.org/10.1074/jbc.C100325200