通过可变mRNA剪接产生的非激素结合型c-erbA蛋白对甲状腺激素作用的抑制。

Inhibition of thyroid hormone action by a non-hormone binding c-erbA protein generated by alternative mRNA splicing.

作者信息

Koenig R J, Lazar M A, Hodin R A, Brent G A, Larsen P R, Chin W W, Moore D D

机构信息

Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.

出版信息

Nature. 1989 Feb 16;337(6208):659-61. doi: 10.1038/337659a0.

DOI:10.1038/337659a0

PMID:2537467

Abstract

Thyroid hormone (T3) binds to a nuclear receptor protein which regulates gene expression by binding to specific DNA sequences near hormone-responsive genes. Proteins encoded by two cellular proto-oncogenes, c-erbA alpha and beta, bind T3 and can act as functional T3 receptors. In rats, alternative splicing of the alpha-gene transcript generates at least two distinct protein products, termed r-erbA alpha 1 and r-erbA alpha 2. Although these proteins bind to the same DNA sequence, r-erbA alpha 2 does not bind T3. We show here that expression of r-erbA alpha 2 inhibits the T3-dependent inductive effect of either r-erbA beta or r-erbA alpha 1 on expression of a T3-responsive test gene. Alternative splicing of the erbA alpha transcript thus generates products with opposing biological activities, suggesting a novel mechanism for the modulation of hormonal responsiveness.

摘要

甲状腺激素（T3）与一种核受体蛋白结合，该蛋白通过与激素反应基因附近的特定DNA序列结合来调节基因表达。两种细胞原癌基因c-erbAα和β编码的蛋白质可结合T3，并可作为功能性T3受体。在大鼠中，α基因转录本的可变剪接产生至少两种不同的蛋白质产物，称为r-erbAα1和r-erbAα2。尽管这些蛋白质与相同的DNA序列结合，但r-erbAα2不结合T3。我们在此表明，r-erbAα2的表达抑制了r-erbAβ或r-erbAα1对T3反应性测试基因表达的T3依赖性诱导作用。因此，erbAα转录本的可变剪接产生了具有相反生物学活性的产物，提示了一种调节激素反应性的新机制。