title: Reconstruction and crosstalk of protein-protein interaction networks of Wnt and Hedgehog signaling in Drosophila melanogaster.
abstract: In the last few years, researchers have an intense interest in the evolutionarily conserved signaling pathways which have crucial roles during embryonic development. The most intriguing factor of this interest is that malfunctioning of these signaling pathways (Hedgehog, Notch, Wnt etc.) leads to several human diseases, especially to cancer. This study deals with the β-catenin dependent branch of Wnt signaling and the Hedgehog signaling pathways which offer potential targeting points for cancer drug development. The identification of all proteins functioning in these signaling networks is crucial for the efforts of preventing tumor formation. Here, through integration of protein-protein interaction data and Gene Ontology annotations, Wnt/β-catenin and Hedgehog signaling networks consisting of proteins that have statistically high probability of being biologically related to these signaling pathways were reconstructed in Drosophila melanogaster. Next, by the structural network analyses, the crucial components functioning in these pathways were identified. The proteins Arm, Frizzled receptors (Fz and Fz2), Arr, Apc, Axn, Ci and Ptc were detected as the key proteins in these networks. Futhermore, the hub protein Mer having tumor suppressor function may be proposed as a putative drug target for cancer and deserves further investigation via experimental methods. Finally, the crosstalk analysis between the reconstructed networks reveals that these two signaling networks crosstalk to each other.
authors: Department of Chemical Engineering, Boğaziçi University, 34342 Bebek-İstanbul, Turkey. ayssuneren@hotmail.com
authors: Aysun Eren
authors: AE
authors: Toku
authors: Saliha Durmuş
authors: SD
authors: Tekir
authors: Fatma Betül Kavun
authors: FB
authors: Özbayraktar
authors: Kutlu Ö
authors: KÖ
authors: Ülgen
mesh_terms: D000818:Animals; D019295:Computational Biology; D030541:Databases, Genetic; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D058977:Molecular Sequence Annotation; D009369:Neoplasms / Q000378:metabolism; D060066:Protein Interaction Maps; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D051153:Wnt Proteins; D051176:beta Catenin