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

Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):18034-9. doi: 10.1073/pnas.0509109102. Epub 2005 Dec 6.

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 TBX5-dependent promoters by interacting with the histone acetyltransferases p300 and PCAF. YAP, a TAZ-related protein with conserved functional domains, also stimulates TBX5-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 TBX5-dependent transcription and suggest the involvement of these coactivators in cardiac and limb development.

Publication types

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

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Acyltransferases
  • Animals
  • Blotting, Western
  • DNA Primers
  • Electrophoretic Mobility Shift Assay
  • Heart Defects, Congenital / genetics*
  • Histone Acetyltransferases
  • Humans
  • Luciferases
  • Mice
  • Plasmids / genetics
  • Proteins / metabolism*
  • RNA Interference
  • Syndrome
  • T-Box Domain Proteins / metabolism*
  • Transcription Factors / metabolism*
  • Transcriptional Activation / genetics*

Substances

  • DNA Primers
  • Proteins
  • T-Box Domain Proteins
  • T-box transcription factor 5
  • Transcription Factors
  • Luciferases
  • Acyltransferases
  • TAFAZZIN protein, human
  • Histone Acetyltransferases