A WW domain protein TAZ is a critical coactivator for TBX5, a transcription factor implicated in Holt-Oram syndrome

Masao Murakami, Masayo Nakagawa, Eric N. Olson, Osamu Nakagawa

Research output: Contribution to journalArticle

178 Scopus citations

Abstract

The T-box transcription factor TBX5 plays essential roles in cardiac and limb development. Various mutations in the TBX5 gene have been identified in patients with Holt-Oram syndrome, which is characterized by congenital defects in the heart and upper extremities. In this study, we identified a WW-domain-containing transcriptional regulator TAZ as a potent TBX5 coactivator. TAZ directly associates with TBX5 and markedly stimulates TBXS-dependent promoters by interacting with the histone acetyltransferases p300 and PCAF. YAP, a TAZ-related protein with conserved functional domains, also stimulates TBXS-dependent transcription, possibly by forming a heterodimer with TAZ. TBX5 lacks a PY motif, which mediates the association of other proteins with TAZ, and interacts with TAZ through multiple domains including its carboxyl-terminal structure. Truncation mutants of TBX5 identified in patients with Holt-Oram syndrome were markedly impaired in their ability to associate with and be stimulated by TAZ. These findings reveal key roles for TAZ and YAP in the control of TBXS-dependent transcription and suggest the involvement of these coactivators in cardiac and limb development.

Original languageEnglish (US)
Pages (from-to)18034-18039
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number50
DOIs
StatePublished - Dec 13 2005

Keywords

  • Hereditary birth defects
  • Organ development
  • Transcriptional coactivator

ASJC Scopus subject areas

  • General

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