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Publication : SETD7 Controls Intestinal Regeneration and Tumorigenesis by Regulating Wnt/β-Catenin and Hippo/YAP Signaling.

First Author  Oudhoff MJ Year  2016
Journal  Dev Cell Volume  37
Issue  1 Pages  47-57
PubMed ID  27046831 Mgi Jnum  J:240229
Mgi Id  MGI:5882675 Doi  10.1016/j.devcel.2016.03.002
Citation  Oudhoff MJ, et al. (2016) SETD7 Controls Intestinal Regeneration and Tumorigenesis by Regulating Wnt/beta-Catenin and Hippo/YAP Signaling. Dev Cell 37(1):47-57
abstractText  Intestinal tumorigenesis is a result of mutations in signaling pathways that control cellular proliferation, differentiation, and survival. Mutations in the Wnt/beta-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 beta-catenin, and SETD7-dependent methylation of YAP facilitates Wnt-induced nuclear accumulation of beta-catenin. Collectively, these results define a methyltransferase-dependent regulatory mechanism that links the Wnt/beta-catenin and Hippo/YAP pathways during intestinal regeneration and tumorigenesis.
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