TEAD transcription factors mediate the function of TAZ in cell growth and epithelial-mesenchymal transition

J Biol Chem. 2009 May 15;284(20):13355-13362. doi: 10.1074/jbc.M900843200. Epub 2009 Mar 26.

Abstract

The TAZ transcription co-activator has been shown to promote cell proliferation and to induce epithelial-mesenchymal transition. Recently we have demonstrated that TAZ is phosphorylated and inhibited by the Hippo tumor suppressor pathway, which is altered in human cancer. The mechanism of TAZ-mediated transcription is unclear. We demonstrate here that TEAD is a key downstream transcription factor mediating the function of TAZ. Disruption of TEAD-TAZ binding or silencing of TEAD expression blocked the function of TAZ to promote cell proliferation and to induce epithelial-mesenchymal transition, demonstrating TEAD as a key downstream effector of TAZ. We also identified CTGF, a gene that regulates cell adhesion, proliferation, and migration, as a direct target of TAZ and TEAD. Our study establishes a functional partnership between TAZ and TEAD under negative regulation by the Hippo signaling pathway.

Publication types

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

MeSH terms

  • Acyltransferases
  • Cell Adhesion / physiology
  • Cell Line
  • Cell Movement / physiology*
  • Cell Proliferation*
  • Connective Tissue Growth Factor / genetics
  • Connective Tissue Growth Factor / metabolism
  • Epithelium / metabolism*
  • Gene Silencing
  • Humans
  • Mesoderm / metabolism*
  • Phosphorylation / physiology
  • Signal Transduction / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism

Substances

  • CCN2 protein, human
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Connective Tissue Growth Factor
  • Acyltransferases
  • TAFAZZIN protein, human