期刊
DEVELOPMENTAL CELL
卷 37, 期 1, 页码 47-57出版社
CELL PRESS
DOI: 10.1016/j.devcel.2016.03.002
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资金
- Australian National Health and Medical Research Council
- Canadian Institutes of Health Research
- Canada Foundation for Innovation grant
- Leon Judah Blackmore Foundation
- CIHR
- Michael Smith Foundation for Health Research (MSFHR)
- Grants-in-Aid for Scientific Research [26115007, 15K08974, 26293177, 15K15297] Funding Source: KAKEN
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. Wehave previously shown thatmethylation 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 ofb-catenin. Collectively, these results define a methyltransferase-dependent regulatory mechanism that links the Wnt/b-catenin and Hippo/YAP pathways during intestinal regeneration and tumorigenesis.
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