INHIBITION OF THYROID-HORMONE ACTION BY A NON-HORMONE BINDING C-ERBA PROTEIN GENERATED BY ALTERNATIVE MESSENGER-RNA SPLICING
INHIBITION OF THYROID-HORMONE ACTION BY A NON-HORMONE BINDING C-ERBA PROTEIN GENERATED BY ALTERNATIVE MESSENGER-RNA SPLICING
复制标题
DOI：
10.1038/337659a0
复制
发表时间：
1989-02-16
期刊：
影响因子：
64.8
通讯作者：
MOORE, DD
中科院分区：
文献类型：
--
作者：
KOENIG, RJ;LAZAR, MA;MOORE, DD
甲状腺激素（T3）与核受体蛋白结合，该蛋白通过结合到免疫应答基因附近的特定DNA序列来调节基因表达1。由两种细胞原癌基因c-erbAα和β编码的蛋白质结合T32，3并可作为功能性T3受体4，5。在大鼠中，α基因转录物的选择性剪接产生至少两种不同的蛋白质产物，称为r-erbAα 1和r-erbAα25-7。虽然这些蛋白质结合相同的DNA序列，但r-erbAα2不结合T3。我们发现r-erbAα2的表达抑制了r-erbAβ或r-erbAα 1对T3反应性测试基因表达的T3依赖性诱导作用。因此，erbA α转录本的选择性剪接产生具有相反生物活性的产物，这表明调节激素反应性的新机制。
Thyroid hormone (T3) binds to a nuclear receptor protein which regulates gene expression by binding to specific DNA sequences near hormone-responsive genes1. Proteins encoded by two cellular proto-oncogenes,c-erbAαandβ, bind T32,3and can act as functional T3 receptors4,5. In rats, alternative splicing of the a-gene transcript generates at least two distinct protein products, termed r-erbAαl and r-erbAα25-7. Although these proteins bind to the same DNA sequence, r-erbAα2 does not bind T3. We show here that expression of r-erbAα2 inhibits the T3-dependent inductive effect of either r-erbAβor r-erbAαl on expression of a T3-responsive test gene. Alternative splicing of theerbAαtranscript thus generates products with opposing biological activities, suggesting a novel mechanism for the modulation of hormonal responsiveness.