PMID- 16332960 OWN - NLM STAT- MEDLINE DCOM- 20060530 LR - 20240314 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 102 IP - 50 DP - 2005 Dec 13 TI - A WW domain protein TAZ is a critical coactivator for TBX5, a transcription factor implicated in Holt-Oram syndrome. PG - 18034-9 AB - 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. FAU - Murakami, Masao AU - Murakami M AD - Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, 75390-9148, USA. FAU - Nakagawa, Masayo AU - Nakagawa M FAU - Olson, Eric N AU - Olson EN FAU - Nakagawa, Osamu AU - Nakagawa O LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20051206 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (DNA Primers) RN - 0 (Proteins) RN - 0 (T-Box Domain Proteins) RN - 0 (T-box transcription factor 5) RN - 0 (Transcription Factors) RN - EC 1.13.12.- (Luciferases) RN - EC 2.3.- (Acyltransferases) RN - EC 2.3.1.- (TAFAZZIN protein, human) RN - EC 2.3.1.48 (Histone Acetyltransferases) SB - IM MH - Abnormalities, Multiple/*genetics MH - Acyltransferases MH - Animals MH - Blotting, Western MH - DNA Primers MH - Electrophoretic Mobility Shift Assay MH - Heart Defects, Congenital/*genetics MH - Histone Acetyltransferases MH - Humans MH - Luciferases MH - Mice MH - Plasmids/genetics MH - Proteins/*metabolism MH - RNA Interference MH - Syndrome MH - T-Box Domain Proteins/*metabolism MH - Transcription Factors/*metabolism MH - Transcriptional Activation/*genetics PMC - PMC1312418 EDAT- 2005/12/08 09:00 MHDA- 2006/05/31 09:00 PMCR- 2006/06/13 CRDT- 2005/12/08 09:00 PHST- 2005/12/08 09:00 [pubmed] PHST- 2006/05/31 09:00 [medline] PHST- 2005/12/08 09:00 [entrez] PHST- 2006/06/13 00:00 [pmc-release] AID - 0509109102 [pii] AID - 18034 [pii] AID - 10.1073/pnas.0509109102 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):18034-9. doi: 10.1073/pnas.0509109102. Epub 2005 Dec 6.