| TAZ (transcriptional coactivator with PDZ-binding motif) is composed of a 14-3-3 binding motif, a WW domain which binds Pro-Pro-X-Tyr motifs, a coiled-coil region within a regulatory domain, multiple phosphorylation sites, and PDZ binding motif at the C-term. The mechanism of regulation of TAZ is not fully understood but involves changes in its expression level, phosphorylation states, and subcellular localization. TAZ has been shown to interact with TEF-1 as well as other transcription factors including Runx2, PPARgamma, and TBX5. TAZ and the related protein YAP65 are strong transcriptional coactivators. YAP/TAZ interact with target proteins in most, but not all cases, through conserved WW domains which bind (A/L/P)PXY motifs in transcription factors. TBX20, a cardiac t-box family member related to TBX5, also contains a PPXY motif similarly to TBX5. This motif potentially can interact with the WW domain in TAZ proteins. Tbx20 is involved in cardiac development and physically interacts with several cardiac specific transcription factors including but not limited to GATA4 and Nkx2. Mutations in this gene has also been identified in individuals diagnosed with Congenital Heart Defects. There are two forms of TBX20, a long(A) and short(B) isoform in which the long form contains the PPXY motif and the short form does not. I have shown, however, that TAZ interacts with both TBX20long and TBX20short, and this interaction is functionally significant. TAZ has also been shown to interact with the TEF-1 protein. The TEF-1 family of proteins has four members including TEF-1(nominal NTEF-1), RTEF-1(Related to TEF-1), DTEF-1(Divergent TEF-1) and ETF-1(Embryonic TEF-1). The TEF-1 family has significant sequence similarity and all bind to (muscle-CAT) MCAT elements (related to CATTCC(A/T)) in different promoters. I have demonstrated, through the use of Immunocytochemistry, that TEF-1 is critical for the increase in cell size during cardiac hypertrophy as well as increase in sarcomeric organization and increase in ANF expression under normal and hypertrophic conditions in neonatal cardiac muscle cells. |
