Ciosk Rafal, DePalma Michael, Priess James R
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Development. 2004 Oct;131(19):4831-41. doi: 10.1242/dev.01352. Epub 2004 Sep 1.
Human ataxin 2 is a protein of unknown function that is implicated in the neurodegenerative disorder spinocerebellar ataxia type 2. We found that the C. elegans ortholog of ataxin 2, ATX-2, forms a complex with PAB-1, a cytoplasmic polyA-binding protein, and that ATX-2 is required for development of the germline. In the absence of ATX-2, proliferation of stem cells is reduced, and the germline is abnormally masculinized. These defects appear to result from inappropriate translational regulation that normally is mediated by the conserved KH-domain protein GLD-1. We find that MEX-3, a second KH-domain protein, exhibits a novel, ATX-2-dependent role in preventing inappropriate translation in the germline stem cells. Together, our results suggest that ATX-2 functions in translational regulation that is mediated by GLD-1 and MEX-3 proteins.
人类ataxin 2是一种功能未知的蛋白质，与神经退行性疾病2型脊髓小脑共济失调有关。我们发现，线虫中ataxin 2的直系同源物ATX-2与一种细胞质多聚腺苷酸结合蛋白PAB-1形成复合物，并且ATX-2是生殖系发育所必需的。在没有ATX-2的情况下，干细胞的增殖减少，生殖系出现异常的雄性化。这些缺陷似乎是由通常由保守的KH结构域蛋白GLD-1介导的不适当的翻译调控导致的。我们发现，另一种KH结构域蛋白MEX-3在防止生殖系干细胞中出现不适当翻译方面发挥了一种新的、依赖于ATX-2的作用。总之，我们的结果表明，ATX-2在由GLD-1和MEX-3蛋白介导的翻译调控中发挥作用。
