Croteau W, Whittemore S L, Schneider M J, St Germain D L
Department of Medicine, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA.
J Biol Chem. 1995 Jul 14;270(28):16569-75. doi: 10.1074/jbc.270.28.16569.
The type III iodothyronine deiodinase metabolizes the active thyroid hormones thyroxine and 3,5,3'-triiodothyronine to inactive compounds. Recently, we have characterized a Xenopus laevis cDNA (XL-15) that encodes a selenoprotein with type III deiodinase activity (St. Germain, D.L., Schwartzman, R., Croteau, W., Kanamori, A., Wang, Z., Brown, D.D., and Galton, V.A. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 7767-7771). Using the XL-15 as a probe, we screened a rat neonatal skin cDNA library. Among the clones isolated was one (rNS43-1) which contained a 2.1-kilobase pair cDNA insert that manifested significant homology to both the XL-15 and the G21 rat type I deiodinase cDNAs, including the presence of an in-frame TGA codon. Expression studies demonstrated that the rNS43-1 cDNA encodes a protein with 5-, but not 5'-, deiodinase activity that is resistant to inhibition by propylthiouracil and aurothioglucose. Northern analysis demonstrated a pattern of tissue expression in the rat consistent with that of the type III deiodinase and site directed mutagenesis confirmed that the TGA triplet codes for selenocysteine. We conclude that the rNS43-1 cDNA encodes the rat type III deiodinase and that the types I and III deiodinases present in amphibians and mammals constitute a family of conserved selenoproteins important in the metabolism of thyroid hormones.
III型碘甲状腺原氨酸脱碘酶将活性甲状腺激素甲状腺素和3,5,3'-三碘甲状腺原氨酸代谢为无活性的化合物。最近，我们鉴定了一种非洲爪蟾cDNA（XL-15），它编码一种具有III型脱碘酶活性的硒蛋白（圣杰曼，D.L.，施瓦茨曼，R.，克罗托，W.，金森，A.，王，Z.，布朗，D.D.，和高尔顿，V.A.（1994年）美国国家科学院院刊91，7767 - 7771）。以XL-15为探针，我们筛选了大鼠新生儿皮肤cDNA文库。在分离出的克隆中，有一个（rNS43-1）包含一个2.1千碱基对的cDNA插入片段，它与XL-15和G21大鼠I型脱碘酶cDNA都表现出显著的同源性，包括存在一个读码框内的TGA密码子。表达研究表明，rNS43-1 cDNA编码一种具有5'-而非5-脱碘酶活性的蛋白质，该活性对丙硫氧嘧啶和金硫葡萄糖的抑制具有抗性。Northern分析显示大鼠组织表达模式与III型脱碘酶一致，定点诱变证实TGA三联体编码硒代半胱氨酸。我们得出结论，rNS43-1 cDNA编码大鼠III型脱碘酶，并且两栖动物和哺乳动物中存在的I型和III型脱碘酶构成了一个在甲状腺激素代谢中起重要作用的保守硒蛋白家族。
