title: APPL1 endocytic adaptor as a fine tuner of Dvl2-induced transcription.
abstract: 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.
authors.affiliation: Laboratory of Cell Biology, International Institute of Molecular and Cell Biology, Warsaw, Poland. Electronic address: magre@iimcb.gov.pl.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Banach-Orlowska
authors.affiliation: Laboratory of Cell Biology, International Institute of Molecular and Cell Biology, Warsaw, Poland.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Szymanska
authors.affiliation: Laboratory of Cell Biology, International Institute of Molecular and Cell Biology, Warsaw, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Miaczynska
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D000072261:Dishevelled Proteins; D011992:Endosomes / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D057809:HEK293 Cells; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D010750:Phosphoproteins / Q000502:physiology*; D025941:Protein Interaction Mapping; D021381:Protein Transport; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D014158:Transcription, Genetic; D060449:Wnt Signaling Pathway
chemical_list: C464801:APPL1 protein, human; D048868:Adaptor Proteins, Signal Transducing; C000606581:DVL2 protein, human; D000072261:Dishevelled Proteins; C000606582:Dvl2 protein, mouse; D010750:Phosphoproteins; D016755:Proto-Oncogene Proteins c-jun; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1
keywords: APPL endocytic proteins; Activating protein 1; Dishevelled; Wnt signaling