WWTR1

WWTR1 contains WW domain, coiled coil region, and PDZ domain-binding motif.

WWTR1 It is a 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. The core of this pathway is composed of a kinase cascade wherein STK3(MST2)/STK4(MST1), in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/LATS2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. WWTR1 enhances PAX8 and NKX2-1(TTF1)-dependent gene activation. Regulates the nuclear accumulation of SMADs and has a key role in coupling them to the transcriptional machinery such as the mediator complex.

Using the human SHSY5Y cell line as a model of neuronal differentiation, human FAT1 was shown to regulate the nucleocytoplasmic relocation of WWTR1/TAZ and enhanced transcription of the Hippo target gene CTGF. The same study also showed FAT1 was able to regulate TGF-beta signalling [8]

Note that this gene is often confused with tafazzin, which has the official gene symbol TAZ. TAZ (the gene) is unrelated to the Hippo pathway. WWTR1 is often referred to as TAZ in research publications due to the first publication describing this gene called it TAZ, even though TAZ (tafazzin) was already named.