Hooper Claudie, Meimaridou Eirini, Tavassoli Mahvash, Melino Gerry, Lovestone Simon, Killick Richard
King's College London, MRC Centre for Neurodegenerative Research, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF, UK.
Neurosci Lett. 2007 May 11;418(1):34-7. doi: 10.1016/j.neulet.2007.03.026. Epub 2007 Mar 15.
p53 and tau are both associated with neurodegenerative disorders. Here, we show by Western blotting that p53 is upregulated approximately 2-fold in the superior temporal gyrus of Alzheimer's patients compared to healthy elderly control subjects. Moreover, p53 was found to induce phosphorylation of human 2N4R tau at the tau-1/AT8 epitope in HEK293a cells. Confocal microscopy revealed that tau and p53 were spatially separated intracellularly. Tau was found in the cytoskeletal compartment, whilst p53 was located in the nucleus, indicating that the effects of p53 on tau phosphorylation are indirect. Collectively, these findings have ramifications for neuronal death associated with Alzheimer's disease and other tauopathies.
p53和tau蛋白均与神经退行性疾病相关。在此,我们通过蛋白质免疫印迹法表明,与健康老年对照受试者相比,阿尔茨海默病患者颞上回中的p53上调了约2倍。此外,在HEK293a细胞中发现p53可诱导人2N4R tau蛋白在tau-1/AT8表位处发生磷酸化。共聚焦显微镜检查显示,tau蛋白和p53在细胞内呈空间分离状态。tau蛋白存在于细胞骨架区室中,而p53位于细胞核内,这表明p53对tau蛋白磷酸化的影响是间接的。总的来说,这些发现对与阿尔茨海默病及其他tau蛋白病相关的神经元死亡具有重要意义。