| Literature DB >> 27184401 |
Carmen Dominguez-Brauer1, Zhenyue Hao1, Andrew J Elia1, Jérôme M Fortin1, Robert Nechanitzky1, Patrick M Brauer2, Yi Sheng3, Miyeko D Mana4, Iok In Christine Chio5, Jillian Haight1, Aaron Pollett6, Robert Cairns1, Leanne Tworzyanski1, Satoshi Inoue1, Colin Reardon7, Ana Marques1, Jennifer Silvester1, Maureen A Cox1, Andrew Wakeham1, Omer H Yilmaz4, David M Sabatini8, Johan H van Es9, Hans Clevers9, Toshiro Sato10, Tak W Mak11.
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.Entities:
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Year: 2016 PMID： 27184401 PMCID： PMC5193118 DOI： 10.1016/j.stem.2016.04.002
Source DB: PubMed Journal: Cell Stem Cell ISSN： 1875-9777 Impact factor: 24.633