Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Curr Alzheimer Res. 2010 Dec;7(8):697-707. doi: 10.2174/156720510793611637.
Microtubule-associated protein tau has long been known for its ability to promote microtubule assembly. A less known feature of tau is its existence as a non-microtubule associated protein. Here we review the interactions of tau with other proteins, some of which interact with the microtubule binding repeat region of tau. The tau interactions with Fyn and with Pin1 have attracted the most attention and both interactions have been thought to have a role in Alzheimer's disease. The fact that tau has unknown cellular functions is further evidenced by its involvement in cell cycle activated neurodegeneration. One possible route for additional investigations stems from the presence of tau in non-neuronal cells where its characteristics have been largely unknown, although there has been a correlation between tau levels and the response of some cancer cells to microtubule-targeting chemotherapy drugs. Our studies of prostate cancer cells indicate that these cells can provide a system with phosphorylated adult tau for functional studies. In fact, structural similarities exist between Alzheimer's disease tau and prostate cancer cell tau, raising the possibility that new tau functions uncovered in prostate cancer cells will have relevance to Alzheimer's disease.
微管相关蛋白 tau 长期以来因其促进微管组装的能力而闻名。tau 的一个不太为人知的特征是它作为非微管相关蛋白的存在。在这里，我们回顾了 tau 与其他蛋白质的相互作用，其中一些与 tau 的微管结合重复区域相互作用。tau 与 Fyn 和 Pin1 的相互作用引起了最多的关注，并且这两种相互作用都被认为在阿尔茨海默病中起作用。tau 具有未知的细胞功能这一事实进一步证明了它参与细胞周期激活的神经退行性变。进一步研究的一个可能途径源于 tau 存在于非神经元细胞中，其特征在很大程度上未知，尽管 tau 水平与一些癌细胞对微管靶向化疗药物的反应之间存在相关性。我们对前列腺癌细胞的研究表明，这些细胞可以为功能研究提供具有磷酸化成年 tau 的系统。事实上，阿尔茨海默病 tau 和前列腺癌细胞 tau 之间存在结构相似性，这增加了在前列腺癌细胞中发现的新 tau 功能与阿尔茨海默病相关的可能性。
