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Polymorphism of Homopolymeric Glutamines in Coactivators for Nuclear Hormone Receptors

机译:核激素受体共活化剂中均聚谷氨酰胺的多态性

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References(28) Cited-By(7) Some of the recently identified coactivators which interact with members of nuclear hormone receptors contain a stretch of homopolymeric glutamines (poly-Q). Length of poly-Q in several genes are known to be polymorphic in healthy subjects, and extraordinary expansion of poly-Q in specific genes is known to cause neurodegenerative disorders. In the present study, we investigated whether such polymorphism can be observed in two Coactivators, CBP (CREB [cyclic AMP responsive element binding protein]-binding protein) and AIB1/ACTR (amplified in breast cancer-1/ACTR, also called RAC3/TRAM-1). The genomic regions encoding the poly-Q were amplified by means of PCR using fluorescence labeled primer and analyzed by an automatic sequencer. While contiguous glutamine residues inAIB1/ACTR ranged from 26 to 32 with a heterozygosity of 54%, no polymorphism could be observed in poly-Q of CBP among 54 unrelated subjects. These results suggest that the residue in CBP may play a critical role in the function so that individuals with CBP containing different sizes of poly-Q might have been eliminated. It has been reported that AIB1/ACTR is overexpressed in some of the cell lines derived from breast cancer. If the length of poly-Q alters the stability of AIB1/ACTR and/or potency to enhance hormone action through nuclear receptors, the length of poly-Q is likely to be one of the genetic factors affecting not only susceptibility to breast cancers but also the sensitivity to hormones. This polymorphism should also be tested in patients with neurodegenerative disorders of unknown cause.
机译:参考文献(28)被引用的依据(7)与核激素受体成员相互作用的一些最近鉴定的共激活剂包含一系列均聚物谷氨酰胺(poly-Q)。已知几个基因中的poly-Q的长度在健康受试者中是多态的,已知特定基因中poly-Q的异常扩增会引起神经退行性疾病。在本研究中,我们调查了是否可以在两种共激活因子CBP(CREB(环AMP响应元件结合蛋白)结合蛋白)和AIB1 / ACTR(在乳腺癌-1 / ACTR,也称为RAC3 / TRAM-1)。使用荧光标记的引物通过PCR扩增编码poly-Q的基因组区域,并通过自动测序仪进行分析。虽然AIB1 / ACTR中的连续谷氨酰胺残基范围为26至32,杂合度为54%,但在54名无关受试者中CBP的poly-Q中未观察到多态性。这些结果表明,CBP中的残基可能在功能中起关键作用,因此可能已淘汰了CBP中含有不同大小的poly-Q的个体。据报道,在一些源自乳腺癌的细胞系中,AIB1 / ACTR过度表达。如果poly-Q的长度改变了AIB1 / ACTR的稳定性和/或通过核受体增强激素作用的能力,那么poly-Q的长度很可能是不仅影响乳腺癌易感性而且还影响乳腺癌易感性的遗传因素之一。对激素的敏感性。这种多态性也应在原因未知的神经退行性疾病患者中进行测试。

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