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PMID: 16332960 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 102 ·No. 50 ·2005-12-13 ·Pages 18034-9

Murakami M, Nakagawa M, Olson EN, Nakagawa O

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.

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
Chemicals
DNA Primers Proteins T-Box Domain Proteins T-box transcription factor 5 Transcription Factors Luciferases Acyltransferases TAFAZZIN protein, human Histone Acetyltransferases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Murakami Masao
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, 75390-9148, USA.
Nakagawa Masayo
Olson Eric N
Nakagawa Osamu
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0509109102
Published
2005-12-13
Epub
2005-00-06
Pages
18034-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1312418
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.0509109102 PMC Full Text View journal details
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