TAZ (WWTR1)
TAZ (transcriptional coactivator with PDZ-binding motif), encoded by WWTR1, is a transcriptional coactivator of the Hippo pathway and the functional partner of YAP1.
Function
TAZ responds to the same signals as YAP: Hippo-pathway kinase activity (LATS1/2) phosphorylates it and keeps it outside the nucleus; cell density, stiff extracellular matrix, and cytoskeletal tension dephosphorylate it and send it in. In the nucleus TAZ partners with TEAD transcription factors to drive proliferation, matrix-remodeling, and stemness genes. The two coactivators have overlapping but distinguishable target preferences - TAZ is the stronger activator of the mesenchymal and matrix-remodeling program - and many tissues express both, with the ratio shifting during differentiation.
In cancer
The WWTR1 locus participates in a defining translocation: WWTR1-CAMTA1, the signature fusion of epithelioid hemangioendothelioma, fuses TAZ’s TEAD-binding region to a transcriptional repressor and creates a constitutive activator. TAZ amplification and nuclear accumulation recur in breast cancer, where TAZ drives metastasis and therapy resistance, and in lung adenocarcinoma. Like YAP, TAZ has no approved direct inhibitor; the therapeutic target is the TEAD interaction.
Notes
- Human gene symbol: WWTR1; UniProt Q9GZV5; 420 amino acids; TEAD-binding and PDZ-binding domains; 14-3-3 binding site at Ser89.