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SETD7 Controls Intestinal Regeneration and Tumorigenesis by Regulating Wnt/ß-Catenin and Hippo/YAP Signaling.
Oudhoff, Menno J; Braam, Mitchell J S; Freeman, Spencer A; Wong, Denise; Rattray, David G; Wang, Jia; Antignano, Frann; Snyder, Kimberly; Refaeli, Ido; Hughes, Michael R; McNagny, Kelly M; Gold, Michael R; Arrowsmith, Cheryl H; Sato, Toshiro; Rossi, Fabio M V; Tatlock, John H; Owen, Dafydd R; Brown, Peter J; Zaph, Colby.
Afiliación
  • Oudhoff MJ; The Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada. Electronic address: menno.oudhoff@ntnu.no.
  • Braam MJS; The Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • Freeman SA; Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • Wong D; The Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • Rattray DG; The Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • Wang J; Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • Antignano F; The Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • Snyder K; The Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • Refaeli I; The Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • Hughes MR; The Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • McNagny KM; The Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • Gold MR; Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • Arrowsmith CH; The Structural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, Canada; Princess Margaret Cancer Centre, University of Toronto, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada.
  • Sato T; Department of Gastroenterology, School of Medicine, Keio University, Tokyo 160-8582, Japan.
  • Rossi FMV; The Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • Tatlock JH; Worldwide Medicinal Chemistry, Pfizer Worldwide Research and Development, San Diego, CA 92121, USA.
  • Owen DR; Worldwide Medicinal Chemistry, Pfizer Worldwide Research and Development, Cambridge, MA 02139, USA.
  • Brown PJ; The Structural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, Canada.
  • Zaph C; The Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Monash Biom
Dev Cell ; 37(1): 47-57, 2016 Apr 04.
Article en En | MEDLINE | ID: mdl-27046831
Intestinal tumorigenesis is a result of mutations in signaling pathways that control cellular proliferation, differentiation, and survival. Mutations in the Wnt/ß-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 ß-catenin, and SETD7-dependent methylation of YAP facilitates Wnt-induced nuclear accumulation of ß-catenin. Collectively, these results define a methyltransferase-dependent regulatory mechanism that links the Wnt/ß-catenin and Hippo/YAP pathways during intestinal regeneration and tumorigenesis.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Fosfoproteínas / Proteína Metiltransferasas / Transformación Celular Neoplásica / Proteínas Adaptadoras Transductoras de Señales / Proteínas Wnt / Beta Catenina / Neoplasias Intestinales Límite: Animals / Humans Idioma: En Revista: Dev Cell Asunto de la revista: EMBRIOLOGIA Año: 2016 Tipo del documento: Article
Texto completo
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Fosfoproteínas / Proteína Metiltransferasas / Transformación Celular Neoplásica / Proteínas Adaptadoras Transductoras de Señales / Proteínas Wnt / Beta Catenina / Neoplasias Intestinales Límite: Animals / Humans Idioma: En Revista: Dev Cell Asunto de la revista: EMBRIOLOGIA Año: 2016 Tipo del documento: Article