@article {Gultekin296830, author = {Yetis Gultekin and Hermann Steller}, title = {Axin proteolysis by Iduna is required for the regulation of stem cell proliferation and intestinal homeostasis in Drosophila}, elocation-id = {296830}, year = {2018}, doi = {10.1101/296830}, publisher = {Cold Spring Harbor Laboratory}, abstract = {The self-renewal of intestinal stem cell is controlled by Wingless/Wnt-β catenin signaling both in Drosophila and mammals. Axin is a rate-limiting factor in wingless signaling. Hence, its regulation is essential. Iduna is an evolutionarily conserved ubiquitin E3 ligase that has been identified as a critical regulator of degradation of ADP-ribosylated Axin and thus of Wnt-β catenin signaling. However, its physiological significance remains to be demonstrated. Here, we generated loss-of-function mutants of Iduna and investigated its physiological role in the Drosophila midgut. Genetic depletion of Iduna causes the accumulation of both Tankyrase and Axin in Drosophila cells. Increase in Axin protein in enterocytes non-autonomously enhanced stem cell divisions. Enterocytes secreted Unpaired and thereby stimulated the activity of the JAK-STAT pathway in intestinal stem cells. A decrease in Axin gene expression suppressed both the over-proliferation of stem cells and restored their numbers to normal levels in Iduna mutants. These findings suggest that Iduna-mediated regulation of Axin proteolysis is essential to maintain tissue homeostasis in the Drosophila midgut.}, URL = {https://www.biorxiv.org/content/early/2018/04/06/296830}, eprint = {https://www.biorxiv.org/content/early/2018/04/06/296830.full.pdf}, journal = {bioRxiv} }