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Mule Regulates the Intestinal Stem Cell Niche via the Wnt Pathway and Targets EphB3 for Proteasomal and Lysosomal Degradation.
Dominguez-Brauer, Carmen; Hao, Zhenyue; Elia, Andrew J; Fortin, Jérôme M; Nechanitzky, Robert; Brauer, Patrick M; Sheng, Yi; Mana, Miyeko D; Chio, Iok In Christine; Haight, Jillian; Pollett, Aaron; Cairns, Robert; Tworzyanski, Leanne; Inoue, Satoshi; Reardon, Colin; Marques, Ana; Silvester, Jennifer; Cox, Maureen A; Wakeham, Andrew; Yilmaz, Omer H; Sabatini, David M; van Es, Johan H; Clevers, Hans; Sato, Toshiro; Mak, Tak W.
Afiliación
  • Dominguez-Brauer C; The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2C1, Canada.
  • Hao Z; The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2C1, Canada.
  • Elia AJ; The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2C1, Canada.
  • Fortin JM; The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2C1, Canada.
  • Nechanitzky R; The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2C1, Canada.
  • Brauer PM; Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada.
  • Sheng Y; Department of Biology, York University, Toronto, ON M3J 1P3, Canada.
  • Mana MD; The David H. Koch Institute of Integrative Cancer Research at MIT, Department of Biology, Cambridge, MA 02139, USA.
  • Chio IIC; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
  • Haight J; The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2C1, Canada.
  • Pollett A; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada.
  • Cairns R; The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2C1, Canada.
  • Tworzyanski L; The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2C1, Canada.
  • Inoue S; The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2C1, Canada.
  • Reardon C; Anatomy, Physiology and Cell Biology, University of California, Davis, Davis, CA 95616, USA.
  • Marques A; The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2C1, Canada.
  • Silvester J; The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2C1, Canada.
  • Cox MA; The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2C1, Canada.
  • Wakeham A; The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2C1, Canada.
  • Yilmaz OH; The David H. Koch Institute of Integrative Cancer Research at MIT, Department of Biology, Cambridge, MA 02139, USA.
  • Sabatini DM; The David H. Koch Institute of Integrative Cancer Research at MIT, Department of Biology, Cambridge, MA 02139, USA; Whitehead Institute for Biomedical Research, Broad Institute, and Howard Hughes Medical Institute, Cambridge, MA 02142, USA.
  • van Es JH; Hubrecht Institute for Developmental Biology and Stem Cell Research and University Medical Centre Utrecht, Uppsalalaan 8, Utrecht 3584 CT, the Netherlands.
  • Clevers H; Hubrecht Institute for Developmental Biology and Stem Cell Research and University Medical Centre Utrecht, Uppsalalaan 8, Utrecht 3584 CT, the Netherlands.
  • Sato T; Department of Gastroenterology, School of Medicine, Keio University, 35 Shinanomachi, Shinnjukuku, Tokyo 160-8582, Japan.
  • Mak TW; The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2C1, Canada. Electronic address: tmak@uhnresearch.ca.
Cell Stem Cell ; 19(2): 205-216, 2016 08 04.
Article en En | MEDLINE | ID: mdl-27184401
ABSTRACT
The E3 ubiquitin ligase Mule is often overexpressed in human colorectal cancers, but its role in gut tumorigenesis is unknown. Here, we show in vivo that Mule controls murine intestinal stem and progenitor cell proliferation by modulating Wnt signaling via c-Myc. Mule also regulates protein levels of the receptor tyrosine kinase EphB3 by targeting it for proteasomal and lysosomal degradation. In the intestine, EphB/ephrinB interactions position cells along the crypt-villus axis and compartmentalize incipient colorectal tumors. Our study thus unveils an important new avenue by which Mule acts as an intestinal tumor suppressor by regulation of the intestinal stem cell niche.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Efrina-B3 / Ubiquitina-Proteína Ligasas / Complejo de la Endopetidasa Proteasomal / Nicho de Células Madre / Proteolisis / Vía de Señalización Wnt / Intestinos / Lisosomas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Stem Cell Año: 2016 Tipo del documento: Article
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Efrina-B3 / Ubiquitina-Proteína Ligasas / Complejo de la Endopetidasa Proteasomal / Nicho de Células Madre / Proteolisis / Vía de Señalización Wnt / Intestinos / Lisosomas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Stem Cell Año: 2016 Tipo del documento: Article