The TEAD/TEF family of transcription factor Scalloped mediates Hippo signaling in organ size control

Dev Cell. 2008 Mar;14(3):377-87. doi: 10.1016/j.devcel.2008.01.006. Epub 2008 Feb 7.

Abstract

The Hippo (Hpo) signaling pathway governs cell growth, proliferation, and apoptosis by controlling key regulatory genes that execute these processes; however, the transcription factor of the pathway has remained elusive. Here we provide evidence that the TEAD/TEF family transcription factor Scalloped (Sd) acts together with the coactivator Yorkie (Yki) to regulate Hpo pathway-responsive genes. Sd and Yki form a transcriptional complex whose activity is inhibited by Hpo signaling. Sd overexpression enhances, whereas its inactivation suppresses, tissue overgrowth caused by Yki overexpression or tumor suppressor mutations in the Hpo pathway. Inactivation of Sd diminishes Hpo target gene expression and reduces organ size, whereas a constitutively active Sd promotes tissue overgrowth. Sd promotes Yki nuclear localization, whereas Hpo signaling retains Yki in the cytoplasm by phosphorylating Yki at S168. Finally, Sd recruits Yki to the enhancer of the pathway-responsive gene diap1, suggesting that diap1 is a direct transcriptional target of the Hpo pathway.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Binding Sites / genetics
  • Cell Line
  • DNA / genetics
  • DNA / metabolism
  • Drosophila / genetics
  • Drosophila / growth & development
  • Drosophila / physiology
  • Drosophila Proteins / genetics
  • Drosophila Proteins / physiology*
  • Enhancer Elements, Genetic
  • Gene Expression Regulation, Developmental
  • Genes, Insect
  • Inhibitor of Apoptosis Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Models, Biological
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology
  • Organ Size / physiology*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / physiology*
  • RNA Interference
  • Signal Transduction / physiology
  • Trans-Activators / genetics
  • Trans-Activators / physiology
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transcription, Genetic
  • Transfection

Substances

  • DIAP1 protein, Drosophila
  • Drosophila Proteins
  • Inhibitor of Apoptosis Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • Trans-Activators
  • Transcription Factors
  • Yki protein, Drosophila
  • sd protein, Drosophila
  • DNA
  • Protein-Serine-Threonine Kinases
  • hpo protein, Drosophila