Carlson Bradley A, Yoo Min-Hyuk, Tsuji Petra A, Gladyshev Vadim N, Hatfield Dolph L
Molecular Biology of Selenium Section, Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Molecules. 2009 Sep 10;14(9):3509-27. doi: 10.3390/molecules14093509.
Selenium (Se) deficiency has been known for many years to be associated with disease, impaired growth and a variety of other metabolic disorders in mammals. Only recently has the major role that Se-containing proteins, designated selenoproteins, play in many aspects of health and development begun to emerge. Se is incorporated into protein by way of the Se-containing amino acid, selenocysteine (Sec). The synthesis of selenoproteins is dependent on Sec tRNA for insertion of Sec, the 21st amino acid in the genetic code, into protein. We have taken advantage of this dependency to modulate the expression of Sec tRNA that in turn modulates the expression of selenoproteins by generating transgenic, conditional knockout, transgenic/standard knockout and transgenic/conditional knockout mouse models, all of which involve the Sec tRNA gene, to elucidate the intracellular roles of this protein class.
多年来人们已经知道,硒(Se)缺乏与哺乳动物的疾病、生长发育受损以及多种其他代谢紊乱有关。直到最近,含硒蛋白质(即硒蛋白)在健康和发育的许多方面所起的主要作用才开始显现出来。硒通过含硒氨基酸硒代半胱氨酸(Sec)掺入蛋白质中。硒蛋白的合成依赖于硒代半胱氨酸转运RNA(Sec tRNA),以便将遗传密码中的第21种氨基酸硒代半胱氨酸插入蛋白质中。我们利用这种依赖性来调节Sec tRNA的表达,进而通过构建转基因、条件性敲除、转基因/标准敲除和转基因/条件性敲除小鼠模型来调节硒蛋白的表达,所有这些模型都涉及Sec tRNA基因,以阐明这类蛋白质在细胞内的作用。