Wbp2 cooperates with Yorkie to drive tissue growth downstream of the Salvador-Warts-Hippo pathway

Abstract

The Salvador-Warts-Hippo (SWH) pathway is a key controller of tissue growth in both flies and mammals, and deregulation of pathway activity contributes to tumour formation. The SWH pathway regulates cell growth, proliferation and apoptosis by restricting activity of the Yorkie transcriptional co-activator protein. The proteins that function together with Yorkie to drive transcription and tissue growth are beginning to be revealed and include the Scalloped (Sd), Teashirt (Tsh) and Homothorax (Hth) transcription factors. In this study, we define Wbp2 as a promoter of Yorkie-dependent growth of Drosophila melanogaster tissues. Mammalian WBP2 was previously identified as a protein that interacts with the mammalian Yorkie homologue, Yes-associated protein. WBP2 has been shown to enhance steroid hormone-dependent transcription in cultured cells but its in vivo function has remained obscure. We show that D. melanogaster Wbp2 interacts with Yorkie in a WW domain-and PY motif-dependent manner and that Wbp2 can enhance Yorkie's transcriptional co-activator properties. In vivo, Wbp2 is required for growth of the D. melanogaster wing, and reduction of Wbp2 expression suppresses overgrowth of tissues that lack the warts growth-suppressive gene. Collectively, these studies define an important role for Wbp2 as a downstream component of the SWH tissue growth-control pathway. © 2011 Macmillan Publishers Limited All rights reserved.