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Research:

Identification and characterization of novel molecules interacting with the downstream Wnt/beta-catenin pathway during cancer signaling

The Wnt/beta-Catenin pathway regulates cell fate decisions during development of vertebrates and invertebrates. Wnt is a secreted glycoprotein that binds to Frizzled receptors. Beta-catenin is a multifunctional adaptor protein/transcription factor that is deregulated in many cancers. In the absence of Wnt binding (off-state), beta-catenin is down-regulated via a degradation complex including GSK-3, CK1, Axin, APC, and PP2A. Processive phosphorylation by CK1 and GSK-3 leads to ubiquitination and proteasomal degradation. In the presence of Wnt binding (on-state), Dishevelled (Dsh) is activated, at least in part by phosphorylation. Activated Dsh is part of a protein complex that recruits GSK-3 away from the degradation complex, allowing the dephosphorylation and nuclear import of beta-catenin and subsequent gene induction via binding to LEF/TCF. Several molecules in this pathway are associated with several different carcinomas. Among them, especially beta-catenin accumulation is observed in many cancer cases. Activation and inhibition of a number of target genes, depending on beta-catenin stabilization are the key points in these carcinomas. The genes with differential expression upon overexpression of S33Y-beta-catenin mutant, have been determined in a SAGE study by our group aiming to obtain a collective identification of these target genes. We classified target molecules using bioinformatic approach. To analyse these target molecules we are using in vitro (Q-RT-PCR, colony formation, proliferation etc.) and in vivo (overexspression etc.) techniques. For more information please visit our web site Aklab.boun.edu.tr