WW domain-containing transcription regulator protein 1 also known as WWTR1 and TAZ, is a 44KDa protein that acts as a downstream regulatory target in the Hippo signaling pathway. This protein undergoes post-translational modification and becomes phosphorylated by LATS2 and STK3/MST2. TAZ in its phosphorylated state is functionally inactive and is retained in the cytoplasm. When TAZ is not phosphorylated it can be retained in the nucleus by a protein called MED15. TAZ is highly expressed in cardiac and skeletal muscle, kidney, heart, placenta and lung.
TAZ plays a highly important role in regulating stem cell self-renewal. A study published in Nature Cell Biology (1) demonstrated that a loss of TAZ leads to inhibition of Transforming growth factor beta signalling and differentiation into neuroectorderm lineage. TGFb family members along with Smad transcriptional modulators regulate developmental events. The activation of transcription does not occur when TAZ is absent as Smad complexes do not accumulate in the nucleus and therefore self-renewal cannot occur. TAZ also plays a highly important role in organ size control. The hippo pathway kinase cascade phosphorylates and therefore inhibits TAZ transcription coactivators. This is activated by high cell density in cell culture. The inhibition of TAZ controls the organ from growing too large as it results in apoptosis and also causes repression of cell proliferation.
1. PMID: 18568018
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