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Poster
32

New cell-based HTRF® assays for the exploration of Wnt signaling pathway

Discussion

The hallmark of the canonical Wnt pathway is the accumulation and the translocation of β-catenin into the nucleus. In absence of Wnt signaling, cytoplasmic β-catenin is degraded by a destruction complex, which includes Axin, adenomatosis polyposis coli (APC), protein phosphatase 2A (PP2A), glycogen synthase kinase 3 (GSK3) and casein kinase 1α (CK1α). Within this complex, Phosphorylation of β-catenin by GSK3 drives it to ubiquitiation and degradation processes. Conversely, binding of Wnt to its frizzled receptor leads to the disruption of the destruction complex, inducing the translocation of β-catenin into the nucleus where it activates the transcription of genes involved in oncogenesis such as cyclin D1 or c-myc. Moreover, mutations in the APC gene is responsible for colorectal cancers. Thus dissecting and understanding the molecular mechanisms implicated in the regulation of the Wnt signaling pathway might provide some clues for the development of therapeutics.

Here we introduce a new HTRF cell-based assays to monitor the phosphorylation and the expression status of key players in Wnt signaling, GSK3 and β-catenin.

Romier M, Costy C, Chouvet C, Oberleitner S, Trinquet E, Charrier-Savournin F.

Cisbio Bioassays, Codolet

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