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PMID:16332960
| Citation |
Murakami, M, Nakagawa, M, Olson, EN and Nakagawa, O (2005) 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. 102:18034-9 |
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| 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. |
| Links |
PubMed PMC1312418 Online version:10.1073/pnas.0509109102 |
| Keywords |
Abnormalities, Multiple/genetics; 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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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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