The two most common alleles of the coding GGN repeat in the androgen receptor gene cause differences in protein function
The two most common alleles of the coding GGN repeat in the androgen receptor gene cause differences in protein function
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DOI：
10.1677/jme-06-0072
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发表时间：
2007-07-01
影响因子：
3.5
通讯作者：
Hillmer, Axel M.
中科院分区：
文献类型：
--
作者：
Brockschmidt, Felix F.;Noethen, Markus M.;Hillmer, Axel M.
遗传学研究报告了雄激素受体（AR）基因外显子1中编码多聚甘氨酸的GGN重复序列与常见人类性状的相关性。聚甘氨酸道位于AR蛋白的反式激活结构域，表明重复序列长度对受体功能的影响。在这里，我们比较了两个最常见的等位基因（23和24重复）和两个极端的等位基因（110和27重复）在HeLa细胞中的报告基因测定的功能特性。观察到重复序列长度与AR活性之间的相关性。这可归因于通过ELISA测定的较高蛋白浓度和长重复等位基因的较高每蛋白活性。有趣的是，蛋白质浓度不相关的转录本数量，通过实时PCR测定，并没有重复长度对蛋白质稳定性的影响，可以检测到在翻译抑制试验。这可能表明重复序列长度影响翻译效率。总之，我们的数据提供了AR GGN重复的两个最常见的等位基因之间的功能差异的证据，支持其在人类性状的发展中的潜在作用。
Genetic studies have reported association of a polyglycine-encoding GGN repeat in exon 1 of the androgen receptor (AR) gene with common human traits. The polyglycine tract is located in the transactivating domain of the AR protein, suggesting an effect of repeat length on receptor function. Here, we compare the functional characteristics of the two most common alleles (23 and 24 repeats) and two extreme alleles (110 and 27 repeats) in a reporter gene assay in HeLa cells. A correlation between the repeat length and AR activity was observed. This is attributable to both a higher protein concentration, determined by ELISA, and a higher per-protein activity of long repeat alleles. Interestingly, protein concentration does not correlate with transcript quantity, determined by real-time PCR assays, and no influence of repeat length on protein stability could be detected in translation inhibition assays. This may suggest that repeat length affects translation efficiency. In conclusion, our data provide evidence of functional differences between the two most common alleles of the AR GGN repeat, supporting its potential role in the development of human traits.