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TAZ promotes cell proliferation and epithelial-mesenchymal transition and is inhibited by the hippo pathway.

TAZ is a WW domain containing a transcription coactivator that modulates mesenchymal differentiation and development of multiple organs. In this study, we show that TAZ is phosphorylated by the Lats tumor suppressor kinase, a key component of the Hippo pathway, whose alterations result in organ and tissue hypertrophy in Drosophila and contribute to tumorigenesis in humans. Lats phosphorylates TAZ on several serine residues in the conserved HXRXXS motif and creates 14-3-3 binding sites, leading to cytoplasmic retention and functional inactivation of TAZ. Ectopic expression of TAZ stimulates cell proliferation, reduces cell contact inhibition, and promotes epithelial-mesenchymal transition (EMT). Elimination of the Lats phosphorylation sites results in a constitutively active TAZ, enhancing the activity of TAZ in promoting cell proliferation and EMT. Our results elucidate a molecular mechanism for TAZ regulation and indicate a potential function of TAZ as an important target of the Hippo pathway in regulating cell proliferation tumorigenesis.

Pubmed ID: 18227151


  • Lei QY
  • Zhang H
  • Zhao B
  • Zha ZY
  • Bai F
  • Pei XH
  • Zhao S
  • Xiong Y
  • Guan KL


Molecular and cellular biology

Publication Data

April 10, 2008

Associated Grants


Mesh Terms

  • 14-3-3 Proteins
  • Amino Acid Motifs
  • Cell Cycle Proteins
  • Cell Division
  • Cell Line, Tumor
  • Cell Movement
  • Cell Transdifferentiation
  • Cell Transformation, Neoplastic
  • Conserved Sequence
  • Drosophila Proteins
  • Epithelial Cells
  • Humans
  • Membrane Proteins
  • Mesoderm
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Protein-Serine-Threonine Kinases
  • Proteins
  • Proto-Oncogene Proteins
  • Receptor Protein-Tyrosine Kinases
  • Recombinant Fusion Proteins
  • Transcription Factors
  • Transcription, Genetic
  • Transferases (Other Substituted Phosphate Groups)