A screen for conditional growth suppressor genes identifies the Drosophila homolog of HD-PTP as a regulator of the oncoprotein Yorkie

• Type of Material: Article
• Authors: M. Melissa Gilbert, Emory University; Marla Tipping, University of Massachusetts; Alexey Veraksa, University of Massachusetts; Kenneth H Moberg, Emory University
• Language: English
• Date: 2011-05-17
• Publisher: Elsevier (Cell Press)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2011 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.devcel.2011.04.012
• Title of Journal or Parent Work: Developmental Cell
• ISSN: 1534-5807
• Volume: 20
• Issue: 5
• Start Page: 700
• End Page: 712
• Grant/Funding Information: This work was supported by NIH CA1123368 to KHM and NSF 0640700 to AV.
• Keywords: Yorkie; growth; Myopic; Hippo; endosome
• Research Categories: Biology, Cell

Abstract

Mammalian cancers depend on ‘multiple hits’, some of which promote growth, and some of which block apoptosis. We screened for mutations that require a synergistic block in apoptosis to promote tissue overgrowth, and identified myopic, the Drosophila homolog of the candidate tumor-suppressor and endosomal regulator His-domain-protein-tyrosine-phosphatase (HD-PTP). We find that Myopic regulates the Sav/Wts/Hpo (SWH) tumor suppressor pathway: Myopic PPxY motifs bind conserved residues in the WW domains of the transcriptional co-activator Yorkie and Myopic colocalizes with Yorkie at endosomes. Myopic controls Yorkie endosomal association and protein levels, ultimately influencing expression of some Yorkie target genes. However, the anti-apoptotic gene diap1 is not affected, which may explain the conditional nature of the myopic growth-phenotype. These data establish Myopic as a Yorkie-regulator and implicate Myopic-dependent association of Yorkie with endosomal compartments as a regulatory step in nuclear outputs of the SWH pathway.