The Hippo Pathway and YAP/TAZ-TEAD Protein-Protein Interaction as Targets for Regenerative Medicine and Cancer Treatment

J Med Chem. 2015 Jun 25;58(12):4857-73. doi: 10.1021/jm501615v. Epub 2015 Mar 11.


The Hippo pathway is an important organ size control signaling network and the major regulatory mechanism of cell-contact inhibition. Yes associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are its targets and terminal effectors: inhibition of the pathway promotes YAP/TAZ translocation to the nucleus, where they interact with transcriptional enhancer associate domain (TEAD) transcription factors and coactivate the expression of target genes, promoting cell proliferation. Defects in the pathway can result in overgrowth phenotypes due to deregulation of stem-cell proliferation and apoptosis; members of the pathway are directly involved in cancer development. The pharmacological regulation of the pathway might be useful in cancer prevention, treatment, and regenerative medicine applications; currently, a few compounds can selectively modulate the pathway. In this review, we present an overview of the Hippo pathway, the sequence and structural analysis of YAP/TAZ, the known pharmacological modulators of the pathway, especially those targeting YAP/TAZ-TEAD interaction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Sequence
  • Animals
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Drug Discovery
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Targeted Therapy* / methods
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Phosphoproteins / chemistry
  • Phosphoproteins / metabolism*
  • Protein Interaction Maps / drug effects
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / metabolism*
  • Regenerative Medicine* / methods
  • Sequence Alignment
  • Signal Transduction / drug effects
  • Stem Cells / metabolism
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism*


  • Adaptor Proteins, Signal Transducing
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Phosphoproteins
  • TAZ protein, human
  • TEAD1 protein, human
  • Transcription Factors
  • YAP1 (Yes-associated) protein, human
  • Hippo protein, human
  • Protein-Serine-Threonine Kinases