POSH regulates Hippo signaling through ubiquitin-mediated expanded degradation
Xianjue Ma, Xiaowei Guo, Helena E Richardson, Tian Xu, Lei Xue
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | NATL ACAD SCIENCES | Published : 2018
The Hippo signaling pathway is a master regulator of organ growth, tissue homeostasis, and tumorigenesis. The activity of the Hippo pathway is controlled by various upstream components, including Expanded (Ex), but the precise molecular mechanism of how Ex is regulated remains poorly understood. Here we identify Plenty of SH3s (POSH), an E3 ubiquitin ligase, as a key component of Hippo signaling in DrosophilaPOSH overexpression synergizes with loss of Kibra to induce overgrowth and up-regulation of Hippo pathway target genes. Furthermore, knockdown of POSH impedes dextran sulfate sodium-induced Yorkie-dependent intestinal stem cell renewal, suggesting a physiological role of POSH in modulati..View full abstract
Awarded by National Natural Science Foundation of China
Awarded by Shanghai Committee of Science and Technology
We thank Duojia Pan, Shian Wu, Georg Halder, Iswar Hariharan, Zhiheng Xu, Jin Jiang, Peter Bryant, Richard Fehon, Bruce Hay, Renjie Jiao, Lei Zhang, Sean Sweeney, Elisabeth Knust, the Bloomington Stock Center, the Vienna Drosophila RNAi Center, and the Core Facility of Drosophila Resource and Technology, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, for providing fly stocks and reagents; Jianzhong Yu and Yonggang Zheng for suggestions; and Brandon Dunn for critical reading of and suggestions regarding the manuscript. This research was supported by National Natural Science Foundation of China Grants 31571516 and 31771595 (to L.X.) and 31601024 (to X.M.) and by Shanghai Committee of Science and Technology Grant 09DZ2260100 (to L.X.). Part of the work was conducted in the laboratory of Duojia Pan at the Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine. T.X. is a Howard Hughes Medical Institute Investigator. H.E.R is supported by La Trobe University.