Mule Regulates the Intestinal Stem Cell Niche via the Wnt Pathway and Targets EphB3 for Proteasomal and Lysosomal Degradation

Dominguez-Brauer, C., Hao, Z., Elia, A. J., Fortin, J. M., Nechanitzky, R., Brauer, P. M., Sheng, Y., Mana, M. D., Chio, II, Haight, J., Pollett, A., Cairns, R., Tworzyanski, L., Inoue, S., Reardon, C., Marques, A., Silvester, J., Cox, M. A., Wakeham, A., Yilmaz, O. H., Sabatini, D. M., van Es, J. H., Clevers, H., Sato, T., Mak, T. W. (August 2016) Mule Regulates the Intestinal Stem Cell Niche via the Wnt Pathway and Targets EphB3 for Proteasomal and Lysosomal Degradation. Cell Stem Cell, 19 (2). pp. 205-16. ISSN 1875-9777 (Electronic)

URL: http://www.ncbi.nlm.nih.gov/pubmed/27184401
DOI: 10.1016/j.stem.2016.04.002

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.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > Myc
diseases & disorders > cancer > cancer types > colon cancer
diseases & disorders > cancer > cancer types > colon cancer

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > ubiquitin ligase
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > Wnt
CSHL Authors:
Communities: CSHL labs > Tuveson lab
Depositing User: Matt Covey
Date: 4 August 2016
Date Deposited: 25 May 2016 14:28
Last Modified: 21 Jul 2017 19:48
PMCID: PMC5193118
Related URLs:
URI: http://repository.cshl.edu/id/eprint/32804

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