Shen Y, Peterson A S
Department of Neurology, University of California at San Francisco, San Francisco, CA 94158, USA.
Cell Mol Life Sci. 2009 Feb;66(3):437-46. doi: 10.1007/s00018-008-8403-9.
The Atrophins are a widely expressed family of transcriptional co-regulators found in all metazoans. Atrophin1 was first identified as a neurodegenerative disease gene whereas Atrophin2 was identified based on homology. Phylogenetic studies indicate that the primordial Atrophin was an Atrophin2 type of gene and Atrophin2 has critical functions in normal mouse embryonic development whereas Atrophin1 is dispensable. Atrophins can interact with a wide range of proteins including membrane receptors, nuclear hormone receptors and other DNA binding transcription factors and can shuttle between the cytoplasm and the nucleus. In the nucleus, Atrophins can act as either co-repressors or co-activators and taken together this suggests that they are intermediaries in transcriptional responses to a diverse array of exogenous signals. Despite progress in understanding the normal role of Atrophins, the mechanism whereby mutations in Atrophin1 cause neurodegeneration has remained enigmatic, although most studies have focused on the idea that neurodegeneration is related to inappropriate transcriptional repression.
萎缩蛋白是在所有后生动物中广泛表达的一类转录共调节因子。萎缩蛋白1最初被鉴定为一种神经退行性疾病基因，而萎缩蛋白2是基于同源性鉴定出来的。系统发育研究表明，原始的萎缩蛋白是一种萎缩蛋白2类型的基因，萎缩蛋白2在正常小鼠胚胎发育中具有关键功能，而萎缩蛋白1则是可有可无的。萎缩蛋白可以与多种蛋白质相互作用，包括膜受体、核激素受体和其他DNA结合转录因子，并且可以在细胞质和细胞核之间穿梭。在细胞核中，萎缩蛋白既可以作为共抑制因子，也可以作为共激活因子，综合来看，这表明它们是对多种外源信号进行转录反应的中间介质。尽管在理解萎缩蛋白的正常作用方面取得了进展，但萎缩蛋白1中的突变导致神经退行性变的机制仍然是个谜，尽管大多数研究都集中在神经退行性变与不适当的转录抑制有关这一观点上。
