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A WW domain-containing yes-associated protein (YAP) is a novel transcriptional co-activator.

A protein module called the WW domain recognizes and binds to a short oligopeptide called the PY motif, PPxY, to mediate protein-protein interactions. The PY motif is present in the transcription activation domains of a wide range of transcription factors including c-Jun, AP-2, NF-E2, C/EBPalpha and PEBP2/CBF, suggesting that it plays an important role in transcriptional activation. We show here that mutation of the PY motif in the subregion of the activation domain of the DNA-binding subunit of PEBP2, PEBP2alpha, abolishes its transactivation function. Using yeast two-hybrid screening, we demonstrate that Yes-associated protein (YAP) binds to the PY motif of PEBP2alpha through its WW domain. The C-terminal region of YAP fused to the DNA-binding domain of GAL4 showed transactivation as strong as that of GAL4-VP16. Exogenously expressed YAP conferred transcription-stimulating activity on the PY motif fused to the GAL4 DNA-binding domain as well as to native PEBP2alpha. The osteocalcin promoter was stimulated by exogenous PEBP2alphaA and a dominant negative form of YAP strongly inhibited this activity, suggesting YAP involvement in this promoter activity in vivo. These results indicate that the PY motif is a novel transcription activation domain that functions by recruiting YAP as a strong transcription activator to target genes.

Pubmed ID: 10228168

Authors

  • Yagi R
  • Chen LF
  • Shigesada K
  • Murakami Y
  • Ito Y

Journal

The EMBO journal

Publication Data

May 4, 1999

Associated Grants

None

Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Carrier Proteins
  • Cell Compartmentation
  • Cell Nucleus
  • Cytoplasm
  • DNA-Binding Proteins
  • Fungal Proteins
  • Humans
  • Mice
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation
  • Osteocalcin
  • Phosphoproteins
  • Promoter Regions, Genetic
  • Protein Binding
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • Transcription Factor AP-2
  • Transcription Factors
  • Transcription, Genetic
  • Transcriptional Activation