The WWTR1 gene is located on chromosome 3 at the band 3q25.1 . The gene spans approximately 220,000 base pairs and is composed of multiple exons . The protein encoded by this gene contains a WW domain, which is a conserved sequence motif involved in protein-protein interactions . This domain allows WWTR1 to interact with other proteins and transcription factors, facilitating its role as a transcriptional coactivator .
WWTR1 functions primarily as a transcriptional coactivator, meaning it does not directly bind to DNA but instead interacts with other transcription factors to regulate gene expression . It is a downstream regulatory target in the Hippo signaling pathway, which is essential for controlling organ size and tumor suppression by restricting cell proliferation and promoting apoptosis .
In the Hippo pathway, WWTR1 is phosphorylated and inactivated by the kinase cascade involving STK3/MST2 and STK4/MST1, which in turn activates LATS1/2 . This phosphorylation prevents WWTR1 from entering the nucleus and promoting gene expression . When dephosphorylated, WWTR1 translocates to the nucleus, where it interacts with transcription factors such as PAX8 and NKX2-1/TTF1 to activate gene expression .
WWTR1 is involved in several critical biological processes, including:
Mutations or dysregulation of WWTR1 have been associated with various diseases, including cancer . Its role in the Hippo signaling pathway makes it a potential target for therapeutic interventions aimed at controlling cell proliferation and tumor growth . Additionally, WWTR1 has been implicated in other conditions such as Epithelioid Hemangioendothelioma and Chanarin-Dorfman Syndrome .
Recombinant WWTR1 is produced using recombinant DNA technology, which involves inserting the WWTR1 gene into an expression vector and introducing it into a host cell to produce the protein . This recombinant protein is used in various research applications to study its function, interactions, and potential therapeutic uses .