TEA domain family member 1-4 and Yes-associated protein 1 complex (TEAD-YAP1)

The TEAD1-4–YAP1 protein-protein interaction is a critical downstream effector of the Hippo signaling pathway, which regulates organ size, cell proliferation, and tissue regeneration (Pobbati & Hong, 2013, Theranostics). YAP1 (and its paralog TAZ) acts as a transcriptional co-activator that lacks DNA-binding activity and must bind to TEA domain (TEAD) transcription factors to initiate the expression of genes involved in cell survival and growth (Noland et al., 2016, Structure). In many cancers, particularly those with NF2 mutations or Hippo pathway dysregulation, the TEAD-YAP1 complex is constitutively active, driving oncogenesis, metastasis, and drug resistance (Zhou et al., 2023, Signal Transduction and Targeted Therapy). Therapeutic strategies focus on disrupting this interaction using small molecules that either bind to the TEAD palmitoylation pocket—essential for stability and YAP binding—or directly block the protein-protein interface (Ikena Oncology, 2023). Current clinical candidates like VT3989 and IK-930 are being evaluated primarily in solid tumors like mesothelioma and NF2-deficient cancers, though potential renal toxicity remains a key safety consideration (Vivace Therapeutics, 2023).

Other names

TEAD-YAP complexYAP1-TEAD interactionHippo pathway effector complexYAP/TAZ-TEAD complex

Disruption of the protein-protein interaction between TEAD transcription factors and the YAP1 co-activator, often via binding to the TEAD palmitoylation pocket or the YAP-binding interface.