Βeta-catenin N-terminal domain: An enigmatic region prone to cancer causing mutations

Publication date: July–September 2017 Source:Mutation Research/Reviews in Mutation Research, Volume 773 Author(s): Mohd Saleem Dar, Paramjeet Singh, Riyaz A. Mir, Mohd Jamal Dar The Wnt/β-catenin is a highly conserved signaling pathway involved in cell fate decisions during various stages of development. Dysregulation of canonical Wnt/β-catenin signaling has been associated with various diseases including cancer. β-Catenin, the central component of canonical Wnt signaling pathway, is a multi-functional protein playing both structural and signaling roles. β-Catenin is composed of three distinct domains: N-terminal domain, C-terminal domain and a central armadillo repeat domain. N-terminal domain of β-catenin harbours almost all of the cancer causing mutations, thus deciphering its critical structural and functional roles offers great potential in cancer detection and therapy. Here, in this review, we have collected information from pharmacological analysis, bio-physical and structural studies, molecular modeling, in-vivo and in-vitro assays, and transgenic animal experiments employing various N-terminal domain variants of β-catenin to discuss the interaction of β-catenin with its binding partners that specifically interact with this domain and the implications of these interactions on signaling, cell fate determination, and in tumorigenesis. A thorough understanding of interactions between β-catenin and its binding partners will enable us to more effectively un...
Source: Mutation Research Reviews in Mutation Research - Category: Genetics & Stem Cells Source Type: research