Mule Regulates the Intestinal Stem Cell Niche via the Wnt Pathway and Targets EphB3 for Proteasomal and Lysosomal Degradation
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nihms836180.pdf
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Author(s)
Dominguez-Brauer, Carmen
Hao, Zhenyue
Elia, Andrew J.
Fortin, Jérôme M.
Nechanitzky, Robert
Brauer, Patrick M.
Sheng, Yi
Chio, Iok In Christine
Haight, Jillian
Pollett, Aaron
Date Issued
May 2016
Journal
Cell Stem Cell
Publisher
Elsevier
Citation
Dominguez-Brauer, Carmen et al. “Mule Regulates the Intestinal Stem Cell Niche via the Wnt Pathway and Targets EphB3 for Proteasomal and Lysosomal Degradation.” Cell Stem Cell 19, 2 (August 2016): 205–216 © 2016 Elsevier Inc
Version
Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.STEM.2016.04.002
