Both TEAD-binding and WW domains are required for the growth stimulation and oncogenic transformation activity of yes-associated protein

Bin Zhao, Joungmok Kim, Xin Ye, Zhi Chun Lai, Kun Liang Guan

Research output: Contribution to journalArticlepeer-review

144 Scopus citations

Abstract

The Yes-associated protein (YAP) transcription coactivator is a candidate human oncogene and a key regulator of organ size. It is phosphorylated and inhibited by the Hippo tumor suppressor pathway. TEAD family transcription factors were recently shown to play a key role in mediating the biological functions of YAP. Here, we show that the WW domain of YAP has a critical role in inducing a subset of YAP target genes independent of or in cooperation with TEAD. Mutation of the WW domains diminishes the ability of YAP to stimulate cell proliferation and oncogenic transformation. Inhibition of YAP oncogenic-transforming activity depends on intact serine residues 127 and 381, two sites that could be phosphorylated by the Hippo pathway. Furthermore, genetic experiments in Drosophila support that WW domains of YAP and Yki, the fly YAP homologue, have an important role in stimulating tissue growth. Our data suggest a model in which YAP induces gene expression and exerts its biological functions by interacting with transcription factors through both the TEAD-binding and WW domains.

Original languageEnglish (US)
Pages (from-to)1089-1098
Number of pages10
JournalCancer Research
Volume69
Issue number3
DOIs
StatePublished - Feb 1 2009

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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