APPL1 endocytic adaptor as a fine tuner of Dvl2-induced transcription

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.