Transcriptional enhanced associate domain transcription factor (TEAD)

The Transcriptional enhanced associate domain (TEAD) transcription factors (TEAD1, TEAD2, TEAD3, and TEAD4) are the primary nuclear mediators of the Hippo signaling pathway, a critical regulator of organ size and tissue homeostasis (Zhou et al., 2022, Signal Transduction and Targeted Therapy). TEADs lack intrinsic transcriptional activity and require binding to co-activators, specifically Yes-associated protein (YAP) and Transcriptional co-activator with PDZ-binding motif (TAZ), to drive the expression of genes involved in cell proliferation and survival (Pobbati & Hong, 2020, Trends in Cancer). In various malignancies, such as mesothelioma and NF2-deficient tumors, the Hippo pathway is inactivated, leading to hyperactivation of the YAP/TAZ-TEAD complex and subsequent oncogenesis (Ikena Oncology, 2023). Modern therapeutic approaches target a unique hydrophobic pocket in TEAD that undergoes auto-palmitoylation, a process essential for TEAD stability and its interaction with YAP/TAZ (Vivace Therapeutics, 2023). Small molecule inhibitors targeting this pocket, such as IK-930 and VT-3989, are currently in clinical development to treat YAP/TAZ-dependent cancers (ClinicalTrials.gov, 2024).

Other names

TEA domain family memberTranscriptional enhancer factorTEFTEAD1TEAD2TEAD3TEAD4

Inhibition of TEAD auto-palmitoylation and disruption of the YAP/TAZ-TEAD protein-protein interaction complex.