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Description

WW domain-containing transcription regulator protein 1 (UniProt: Q9EPK5, also known as Transcriptional coactivator with PDZ-binding motif, TAZ) is encoded by the Wwtr1 (also known as Taz) gene (Gene ID: 97064) in murine species. TAZ is an oncogenic transcriptional activator that acts as a downstream regulatory target in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. TAZ is highly expressed in kidney, heart, placenta, and lung tissues. Two isoforms of TAZ have been reported that are produced by alternative splicing. TAZ is concentrated along specific portions of the plasma membrane and also accumulates in punctate nuclear bodies. The ability of TAZ to regulate gene transcription is very tightly regulated through the phosphorylation-dependent binding of 14-3-3 protein. Upon phosphorylation TAZ is retained in cytoplasm by 14-3-3 zeta. Expression of NPHP9 is reported to inhibit the interaction of wild-type TAZ with 14-3-3 and NPHP9 is reported to abolish the phosphorylation of TAZ at Serine 89. TAZ is shown to be involved in non-small-cell lung cancer and its higher expression levels are observed in breast cancer and in breast cancer stem cells. It also regulates embryonic stem-cell self-renewal and promotes cell proliferation and epithelial-mesenchymal transition. TAZ binds to transcription factors via its WW domain, which is localized to amino acids 124-157. Its PZD-binding motif is located in amino acids 389-395 and this motif is essential for stimulated gene transcription.