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

The TAZ-TEAD transcriptional complex is a primary downstream effector of the Hippo signaling pathway, playing a pivotal role in regulating cell proliferation, survival, and stem cell pluripotency (UniProt Q9GZV5; PubMed 30635430). TAZ (Transcriptional coactivator with PDZ-binding motif) serves as a transcriptional coactivator that, upon nuclear translocation, binds to TEA domain (TEAD) family transcription factors to initiate the expression of genes like CTGF and CYR61 involved in cell growth and epithelial-to-mesenchymal transition (PubMed 34634252). In many human malignancies, such as mesothelioma and various carcinomas, the Hippo pathway is inactivated, leading to hyperactivation of the TAZ-TEAD complex which drives tumor progression and therapeutic resistance (PubMed 29123071). Because TEAD proteins require auto-palmitoylation for structural stability and coactivator binding, this pocket has become a key site for small-molecule drug development (PubMed 32814910). Current therapeutic strategies include palmitoylation inhibitors and protein-protein interaction disruptors designed to block TAZ-mediated gene transcription (Ikena Oncology; Novartis). These agents, such as IK-930 and IAG933, are currently being evaluated in clinical trials for patients with Hippo-pathway-altered solid tumors (ClinicalTrials.gov).

Other names

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

Small molecule inhibition of TEAD auto-palmitoylation or direct disruption of the protein-protein interaction between TAZ/YAP and TEAD transcription factors (PubMed 32814910).