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.
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Authors | Masao Murakami, Masayo Nakagawa, Eric N Olson, Osamu Nakagawa |
Journal | Proceedings of the National Academy of Sciences of the United States of America
(Proc Natl Acad Sci U S A)
Vol. 102
Issue 50
Pg. 18034-9
(Dec 13 2005)
ISSN: 0027-8424 [Print] United States |
PMID | 16332960
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- DNA Primers
- Proteins
- T-Box Domain Proteins
- T-box transcription factor 5
- Transcription Factors
- Luciferases
- Acyltransferases
- TAFAZZIN protein, human
- Histone Acetyltransferases
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Topics |
- 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)
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