WWTR1
Description
The WWTR1 (WW domain containing transcription regulator 1) is a protein-coding gene located on chromosome 3.
WWTR1, also known as Transcriptional coactivator with PDZ-binding motif (TAZ), is a protein that is encoded by the WWTR1 gene in humans. WWTR1 functions as a transcriptional coregulator and lacks the ability to directly drive transcription on its own. However, it acts in conjunction with transcription factor binding partners to promote gene expression in pathways related to development, cell growth and survival, and inhibiting apoptosis. Its aberrant function is linked to cancer development. WWTR1 contains a proline-rich region, TEAD binding motif, WW domain, coiled-coil region, and a transactivation domain (TAD) containing the PDZ domain-binding motif. WWTR1 lacks a DNA binding domain, making it reliant on other factors for transcriptional activity. It shares structural similarities with another transcriptional coregulator, yes-associated protein 1 (YAP), and both YAP and TAZ can form homodimers and heterodimers through interactions at their coiled-coil domain. They cooperate with transcription factors to promote tissue formation. WWTR1 interacts with various transcriptional partners, including the four TEA domain family members (TEAD1/2/3/4) through the TEAD-binding motif and several other factors containing the PPXY motif, which is a Proline-Proline-X (any amino acid)-Tyrosine sequence.
WWTR1 is a transcriptional coactivator that acts as a downstream target in the Hippo signaling pathway. This pathway plays a crucial role in regulating organ size and suppressing tumor growth by limiting cell proliferation and promoting apoptosis. The pathway's core involves a kinase cascade where STK3/MST2 and STK4/MST1, in complex with SAV1, phosphorylate and activate LATS1/2 (in complex with MOB1). Subsequently, LATS1/2 phosphorylates and inactivates YAP1 and WWTR1/TAZ. WWTR1 enhances gene activation dependent on PAX8 and NKX2-1/TTF1. In collaboration with YAP1, WWTR1 regulates the nuclear accumulation of SMAD2 and SMAD3, which is dependent on TGFB1. WWTR1 is essential for connecting SMADs with transcriptional machinery like the mediator complex. WWTR1 influences embryonic stem cell self-renewal, promotes cell proliferation, and drives epithelial-mesenchymal transition.
WWTR1 is also known as TAZ.
