Comput Biol Chem - Reconstruction and crosstalk of protein-protein interaction networks of Wnt and Hedgehog signaling in Drosophila melanogaster.

Tópicos

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Resumo

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 ?-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/?-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.

Resumo Limpo

last year research intens interest evolutionarili conserv signal pathway crucial role embryon develop intrigu factor interest malfunct signal pathway hedgehog notch wnt etc lead sever human diseas especi cancer studi deal catenin depend branch wnt signal hedgehog signal pathway offer potenti target point cancer drug develop identif protein function signal network crucial effort prevent tumor format integr proteinprotein interact data gene ontolog annot wntcatenin hedgehog signal network consist protein statist high probabl biolog relat signal pathway reconstruct drosophila melanogast next structur network analys crucial compon function pathway identifi protein arm frizzl receptor fz fz arr apc axn ci ptc detect key protein network futhermor hub protein mer tumor suppressor function may propos putat drug target cancer deserv investig via experiment method final crosstalk analysi reconstruct network reveal two signal network crosstalk

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