| Literature DB >> 27046831 |
Menno J Oudhoff1, Mitchell J S Braam2, Spencer A Freeman3, Denise Wong2, David G Rattray2, Jia Wang3, Frann Antignano2, Kimberly Snyder2, Ido Refaeli2, Michael R Hughes2, Kelly M McNagny4, Michael R Gold3, Cheryl H Arrowsmith5, Toshiro Sato6, Fabio M V Rossi4, John H Tatlock7, Dafydd R Owen8, Peter J Brown9, Colby Zaph10.
Abstract
Intestinal tumorigenesis is a result of mutations in signaling pathways that control cellular proliferation, differentiation, and survival. Mutations in the Wnt/β-catenin pathway are associated with the majority of intestinal cancers, while dysregulation of the Hippo/Yes-Associated Protein (YAP) pathway is an emerging regulator of intestinal tumorigenesis. In addition, these closely related pathways play a central role during intestinal regeneration. We have previously shown that methylation of the Hippo transducer YAP by the lysine methyltransferase SETD7 controls its subcellular localization and function. We now show that SETD7 is required for Wnt-driven intestinal tumorigenesis and regeneration. Mechanistically, SETD7 is part of a complex containing YAP, AXIN1, and β-catenin, and SETD7-dependent methylation of YAP facilitates Wnt-induced nuclear accumulation of β-catenin. Collectively, these results define a methyltransferase-dependent regulatory mechanism that links the Wnt/β-catenin and Hippo/YAP pathways during intestinal regeneration and tumorigenesis.Entities:
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Year: 2016 PMID： 27046831 DOI： 10.1016/j.devcel.2016.03.002
Source DB: PubMed Journal: Dev Cell ISSN： 1534-5807 Impact factor: 12.270