TAZ

The PDZ-binding motif is essential for stimulated gene transcription. It localizes the protein into both punctate nuclear foci and plasma membrane-associated complexes.

Binds to transcription factors via its WW domain.

Transcriptional coactivator which 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 (PubMed:11118213, PubMed:18227151, PubMed:23911299). The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ (PubMed:18227151). WWTR1 enhances PAX8 and NKX2-1/TTF1-dependent gene activation (PubMed:19010321). In conjunction with YAP1, involved in the regulation of TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation (PubMed:18568018). Plays a key role in coupling SMADs to the transcriptional machinery such as the mediator complex (PubMed:18568018). Regulates embryonic stem-cell self-renewal, promotes cell proliferation and epithelial-mesenchymal transition (PubMed:18227151, PubMed:18568018).

Phosphorylated by LATS2 and STK3/MST2. Phosphorylation by LATS2 results in creation of 14-3-3 binding sites, retention in the cytoplasm, and functional inactivation. Phosphorylation results in the inhibition of transcriptional coactivation through YWHAZ-mediated nuclear export. Phosphorylated in the nucleus by PRP4K; phosphorylation leads to nuclear exclusion (PubMed:29695716).

Ubiquitinated at Lys-46; leading to proteasomal degradation. Deubiquitinated and stabilized by UCHL1 at Lys-46; leading to inhibition of osteoclastogenesis.

Highly expressed in kidney, heart, placenta and lung. Expressed in the thyroid tissue.

• Nucleus
• Cytoplasm
• Cell membrane
• Cell junction
• Tight junction
• Concentrates along specific portions of the plasma membrane, and accumulates in punctate nuclear bodies (By similarity). When phosphorylated, is retained in the cytoplasm by YWHAZ (By similarity). Can be retained in the nucleus by MED15 (PubMed:18568018). Localized in the cytoplasm in areas of epithelial cell high density (PubMed:21145499). At blastocyst stage expressed in the nucleus in trophectodermal cells, however expressed in the cytoplasm in the inner cell mass (By similarity). In the nucleus, phosphorylation by PRP4K induces nuclear exclusion (PubMed:29695716). Interaction with AMOTL2 results in localization to the cytoplasm and tight junctions (PubMed:23911299).

TAZ, WWTR1, WW domain-containing transcription regulator protein 1, Transcriptional coactivator with PDZ-binding motif

• entrezGene:25937
• omim:607392
• swissprot:Q9GZV5

Proteins

Oncology

44101Da