Banach-Orlowska Magdalena, Szymanska Ewelina, Miaczynska Marta
Laboratory of Cell Biology, International Institute of Molecular and Cell Biology, Warsaw, Poland.
Laboratory of Cell Biology, International Institute of Molecular and Cell Biology, Warsaw, Poland.
FEBS Lett. 2015 Feb 13;589(4):532-9. doi: 10.1016/j.febslet.2015.01.022. Epub 2015 Jan 23.
APPL1 is a multifunctional endocytic adaptor which acts at different steps of various signaling pathways. Here we report that APPL1 interacts with Dvl2, a protein known to activate the canonical and non-canonical Wnt pathways. APPL1 synergizes with Dvl2 and potentiates transcription driven by AP-1 transcription factors, specifically by c-Jun, in non-canonical Wnt signaling. This function of APPL1 requires its endosomal recruitment. Overproduction of APPL1 increases Dvl2-mediated expression of AP-1 target gene encoding metalloproteinase 1 (MMP1) in a JNK-dependent manner. Collectively, we propose a novel role of APPL1 as a positive regulator of Dvl2-dependent transcriptional activity of AP-1.
APPL1是一种多功能内吞衔接蛋白，在多种信号通路的不同步骤发挥作用。在此我们报告，APPL1与Dvl2相互作用，Dvl2是一种已知可激活经典和非经典Wnt通路的蛋白质。在非经典Wnt信号传导中，APPL1与Dvl2协同作用，并增强由AP-1转录因子（特别是c-Jun）驱动的转录。APPL1的这一功能需要其在内体的募集。APPL1的过量表达以JNK依赖的方式增加Dvl2介导的AP-1靶基因金属蛋白酶1（MMP1）的表达。总体而言，我们提出APPL1作为Dvl2依赖的AP-1转录活性的正调控因子具有新的作用。
