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

作者：Dominguez Brauer Carmen; Hao Zhenyue; Elia Andrew J; Fortin Jerome 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^*

来源：Cell Stem Cell, 2016, 19(2): 205-216.

DOI：10.1016/j.stem.2016.04.002

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.

• 出版日期2016-8-4
• 单位MIT