title: Impaired Hippo signaling promotes Rho1-JNK-dependent growth.
abstract: The Hippo and c-Jun N-terminal kinase (JNK) pathway both regulate growth and contribute to tumorigenesis when dysregulated. Whereas the Hippo pathway acts via the transcription coactivator Yki/YAP to regulate target gene expression, JNK signaling, triggered by various modulators including Rho GTPases, activates the transcription factors Jun and Fos. Here, we show that impaired Hippo signaling induces JNK activation through Rho1. Blocking Rho1-JNK signaling suppresses Yki-induced overgrowth in the wing disk, whereas ectopic Rho1 expression promotes tissue growth when apoptosis is prohibited. Furthermore, Yki directly regulates Rho1 transcription via the transcription factor Sd. Thus, our results have identified a novel molecular link between the Hippo and JNK pathways and implicated the essential role of the JNK pathway in Hippo signaling-related tumorigenesis.
authors.affiliation: Institute of Intervention Vessel, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai 200092, China;
authors.forename: Xianjue
authors.initials: X
authors.lastname: Ma
authors.affiliation: Institute of Intervention Vessel, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai 200092, China;
authors.forename: Yujun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai 200092, China;
authors.forename: Wenyan
authors.initials: W
authors.lastname: Xu
authors.affiliation: Institute of Intervention Vessel, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai 200092, China;
authors.forename: Nana
authors.initials: N
authors.lastname: Wu
authors.affiliation: Institute of Intervention Vessel, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai 200092, China;
authors.forename: Maoquan
authors.initials: M
authors.lastname: Li
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai 200092, China;
authors.forename: Ying
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Genetics and Cell Biology, School of Life Sciences, Nankai University, Tianjin 300071, China; and.
authors.forename: Shian
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Ophthalmology and Visual Sciences, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202.
authors.forename: Qiutang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Institute of Intervention Vessel, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai 200092, China; lei.xue@tongji.edu.cn.
authors.forename: Lei
authors.initials: L
authors.lastname: Xue
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D060227:Imaginal Discs / Q000166:cytology / Q000196:embryology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology; D014921:Wings, Animal / Q000166:cytology / Q000196:embryology*; D000091102:YAP-Signaling Proteins; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000099317:Hippo Kinases
chemical_list: D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D015534:Trans-Activators; D000091102:YAP-Signaling Proteins; D020741:rho GTP-Binding Proteins; C503814:Yki protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases; C511153:Rho1 protein, Drosophila
keywords: Drosophila; Hippo; JNK; Rho1; growth