title: Mutual repression by bantam miRNA and Capicua links the EGFR/MAPK and Hippo pathways in growth control.
abstract: BACKGROUND
  The epidermal growth factor receptor (EGFR) and Hippo signaling pathways control cell proliferation and apoptosis to promote tissue growth during development. Misregulation of these pathways is implicated in cancer. Our understanding of the mechanisms that integrate the activity of these pathways remains fragmentary. This study identifies bantam microRNA as a common target of these pathways and suggests a mechanistic link between them.
  
  
  RESULTS
  The EGFR pathway acts through bantam to control tissue growth. bantam expression is regulated by the EGFR pathway, acting via repression of the transcriptional repressor Capicua. Thus EGFR signaling induces bantam expression by alleviating the effects of a repressor. bantam in turn acts in a negative feedback loop to limit Capicua expression.
  
  
  CONCLUSIONS
  bantam appears to be a transcriptional target of both the EGFR and Hippo growth control pathways. Feedback regulation by bantam on Capicua provides a means to link signal propagation by the EGFR pathway to activity of the Hippo pathway and may play an important role in integration of these two pathways in growth control.
authors.affiliation: Institute of Molecular and Cell Biology, Singapore 138673, Singapore.
authors.forename: Héctor
authors.initials: H
authors.lastname: Herranz
authors.forename: Xin
authors.initials: X
authors.lastname: Hong
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Cohen
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004330:Drosophila / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D025461:Feedback, Physiological; D018507:Gene Expression Regulation, Developmental; D024002:HMGB Proteins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D007814:Larva; D020935:MAP Kinase Signaling System; D035683:MicroRNAs / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D011161:Porifera / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D018010:Receptors, Invertebrate Peptide / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014921:Wings, Animal / Q000254:growth & development / Q000378:metabolism; D000091102:YAP-Signaling Proteins; D000099317:Hippo Kinases
chemical_list: D029721:Drosophila Proteins; D066246:ErbB Receptors; D024002:HMGB Proteins; D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D018010:Receptors, Invertebrate Peptide; D012097:Repressor Proteins; D015534:Trans-Activators; D000091102:YAP-Signaling Proteins; C503814:Yki protein, Drosophila; C471146:bantam microRNA, Drosophila; C404284:cic protein, Drosophila; C066532:Egfr protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases