@article{d55a8493bfa848b09f27bdfbc31d6e6d,
title = "Mule Regulates the Intestinal Stem Cell Niche via the Wnt Pathway and Targets EphB3 for Proteasomal and Lysosomal Degradation",
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.",
author = "Carmen Dominguez-Brauer and Zhenyue Hao and Elia, {Andrew J.} and Fortin, {J{\'e}r{\^o}me M.} and Robert Nechanitzky and Brauer, {Patrick M.} and Yi Sheng and Mana, {Miyeko D.} and Chio, {Iok In Christine} and Jillian Haight and Aaron Pollett and Robert Cairns and Leanne Tworzyanski and Satoshi Inoue and Colin Reardon and Ana Marques and Jennifer Silvester and Cox, {Maureen A.} and Andrew Wakeham and Yilmaz, {Omer H.} and Sabatini, {David M.} and {van Es}, {Johan H.} and Hans Clevers and Toshiro Sato and Mak, {Tak W.}",
note = "Funding Information: This study is dedicated to the memory of C.D.-B.{\textquoteright}s late mother, Maria Gloria Dominguez, who fought a valiant battle against colon cancer. C.D.-B. would like to thank all members of the Mak laboratory for their unstinting support. All authors are grateful to Kyle Gill of the genotyping facility and the animal resource center at the Princess Margaret Hospital (Toronto). Lastly, we thank Dr. Mary Saunders for scientific editing of the manuscript. This work was supported by a grant to T.W.M. from the Canadian Institutes of Health Research (CIHR), a postdoctoral fellowship to C.D.-B. from the Takeda Canada-CIHR-Canadian Association of Gastroenterology, and a postdoctoral fellowship to R.N. from EMBO and Marie Curie (ALTF 725-2015). Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
month = aug,
day = "4",
doi = "10.1016/j.stem.2016.04.002",
language = "English (US)",
volume = "19",
pages = "205--216",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "2",
}