Novel mediators of amyloid precursor protein signaling.
Novel mediators of amyloid precursor protein signaling.
复制标题
DOI：
10.1523/jneurosci.4351-09.2009
复制
发表时间：
2009-12-16
期刊：
影响因子：
--
通讯作者：
Bredesen DE
中科院分区：
文献类型：
--
作者：
Swistowski A;Zhang Q;Orcholski ME;Crippen D;Vitelli C;Kurakin A;Bredesen DE
最近的多项报告表明淀粉样前体蛋白 (APP) 信号传导参与阿尔茨海默病的发病机制，但所涉及的 APP 依赖性信号传导网络尚未明确。在这里，我们报告了与 APP 相互作用蛋白 Mint1、Mint2 和 Mint3（X11α、X11β 和 X11γ）的 PDZ-1 和 PDZ-2 结构域相互作用的新共有序列，以及这些蛋白质的多个新相互作用子，发现转录共激活子在这些相互作用子中具有高度代表性。此外，我们发现 Mint3 与一组转录辅激活因子的相互作用导致核定位和反式激活，而同一组转录辅激活因子与 Mint1 或 Mint2 的相互作用则阻止核定位和反式激活。这些结果定义了 APP 介导的信号转导网络的新介质。
Multiple recent reports implicate amyloid precursor protein (APP) signaling in the pathogenesis of Alzheimer's disease, but the APP-dependent signaling network involved has not been defined. Here we report a novel consensus sequence for interaction with the PDZ-1 and PDZ-2 domains of the APP-interacting proteins Mint1, Mint2, and Mint3 (X11α, X11β, and X11γ), and multiple novel interactors for these proteins, with the finding that transcriptional co-activators are highly represented among these interactors. Furthermore, we show that Mint3 interaction with a set of the transcriptional co-activators leads to nuclear localization and transactivation, whereas interaction of the same set with Mint1 or Mint2 prevents nuclear localization and transactivation. These results define new mediators of the signal transduction network mediated by APP.