Transcriptional coactivator with PDZ-binding motif-TEA domain family member complex (TAZ-TEAD complex) (TAZ-TEAD)

The TAZ-TEAD complex is a central transcriptional regulatory unit of the Hippo signaling pathway, playing a pivotal role in controlling organ size, cell proliferation, and tissue regeneration. TAZ (Transcriptional coactivator with PDZ-binding motif) serves as a transcriptional coactivator that lacks its own DNA-binding domain and must associate with TEA domain (TEAD) transcription factors to initiate the expression of genes such as CTGF and CYR61. Under normal physiological conditions, the Hippo kinase cascade phosphorylates TAZ, leading to its cytoplasmic retention and subsequent degradation. However, in various malignancies, the Hippo pathway is frequently inactivated or bypassed, resulting in the nuclear accumulation of TAZ and the constitutive formation of the TAZ-TEAD complex. This aberrant activation promotes oncogenic phenotypes, including increased cell survival, epithelial-mesenchymal transition (EMT), and resistance to standard therapies. As a result, the TAZ-TEAD interaction is a major focus of drug discovery, with therapeutic strategies aiming to disrupt the protein-protein interface or target the palmitoylation pocket of TEAD to inhibit its activity in cancer cells.

Other names

WWTR1-TEAD complexHippo pathway effector complexTAZ-TEAD1/2/3/4 complex

Inhibition of protein-protein interaction between TAZ/YAP and TEAD; Inhibition of TEAD auto-palmitoylation to prevent complex formation and stability.