Mutual repression by bantam miRNA and Capicua links the EGFR/MAPK and Hippo pathways in growth control

Curr Biol. 2012 Apr 24;22(8):651-7. doi: 10.1016/j.cub.2012.02.050. Epub 2012 Mar 22.

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.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Drosophila / embryology
  • Drosophila / genetics
  • Drosophila / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Embryo, Nonmammalian
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Feedback, Physiological
  • Gene Expression Regulation, Developmental
  • HMGB Proteins / metabolism*
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Larva
  • MAP Kinase Signaling System*
  • MicroRNAs / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Phenotype
  • Porifera / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Receptors, Invertebrate Peptide / genetics
  • Receptors, Invertebrate Peptide / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Signal Transduction
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Wings, Animal / growth & development
  • Wings, Animal / metabolism
  • YAP-Signaling Proteins

Substances

  • Drosophila Proteins
  • HMGB Proteins
  • Intracellular Signaling Peptides and Proteins
  • MicroRNAs
  • Nuclear Proteins
  • Receptors, Invertebrate Peptide
  • Repressor Proteins
  • Trans-Activators
  • YAP-Signaling Proteins
  • Yki protein, Drosophila
  • bantam microRNA, Drosophila
  • cic protein, Drosophila
  • Egfr protein, Drosophila
  • ErbB Receptors
  • Protein Serine-Threonine Kinases
  • hpo protein, Drosophila