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 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 . WWTR1 enhances PAX8 and NKX2-1/TTF1-dependent gene activation . In conjunction with YAP1, involved in the regulation of TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation . Plays a key role in coupling SMADs to the transcriptional machinery such as the mediator complex . Regulates embryonic stem-cell self-renewal, promotes cell proliferation and epithelial-mesenchymal transition (, ).
Subcellular locations: Nucleus, Cytoplasm, Cell membrane
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 . Localized in the cytoplasm in areas of epithelial cell high density . At blastocyst stage expressed in the nucleus in trophectodermal cells, however expressed in the cytoplasm in the inner cell mass (By similarity).
Highly expressed in kidney, heart, placenta and lung. Expressed in the thyroid tissue.