Albrecht Andrea, Mundlos Stefan
Max-Planck Institute for Molecular Genetics, and Institute for Medical Genetics, Charité, Berlin, Germany.
Curr Opin Genet Dev. 2005 Jun;15(3):285-93. doi: 10.1016/j.gde.2005.04.003.
Expansions of trinucleotide repeats encoding polyalanine tracts have been recognized as the cause of several diseases, predominantly congenital malformation syndromes. To date, nine genes with alanine tract expansions have been described. With the exception of PABPN1, which codes for a poly(A)-binding protein, all these genes encode transcription factors that play important roles during development. Recent in vitro and in vivo findings indicate that expansions of polyalanine tracts beyond a certain threshold result in protein misfolding, aggregation and subsequent degradation. Polyalanine tracts are relatively common in the genome and occur most frequently in transcription factors and other proteins with nuclear localization. The molecular role of alanine tracts is unknown, but their strong evolutionary conservation suggests the existence of potent functional or structural constraints.
编码聚丙氨酸序列的三核苷酸重复序列的扩增已被确认为多种疾病的病因，主要是先天性畸形综合征。迄今为止，已描述了9个具有丙氨酸序列扩增的基因。除了编码聚（A）结合蛋白的PABPN1外，所有这些基因都编码在发育过程中起重要作用的转录因子。最近的体外和体内研究结果表明，聚丙氨酸序列扩增超过一定阈值会导致蛋白质错误折叠、聚集和随后的降解。聚丙氨酸序列在基因组中相对常见，最常出现在转录因子和其他具有核定位的蛋白质中。丙氨酸序列的分子作用尚不清楚，但其高度的进化保守性表明存在强大的功能或结构限制。
