Yes-associated protein 1–TEA domain family member transcriptional complex (YAP–TEAD) (YAP–TEAD)

The Yes-associated protein 1 (YAP)–TEA domain family member (TEAD) transcriptional complex is the primary downstream effector of the Hippo signaling pathway, a critical regulator of organ size and tissue homeostasis (PMID: 29123071). YAP and its paralog TAZ function as transcriptional co-activators that do not bind DNA directly; instead, they interact with TEAD family transcription factors (TEAD1–4) to initiate the expression of genes promoting cell survival and proliferation (PMID: 30447558). Dysregulation of this complex, often through mutations in upstream regulators like NF2 or LATS1/2, is a hallmark of various cancers, including mesothelioma and uveal melanoma (PMID: 32814830). Hyperactivation of YAP–TEAD signaling promotes tumor growth, epithelial-to-mesenchymal transition, and resistance to conventional therapies. Pharmacological targeting of the YAP–TEAD complex is an active area of oncology research, with strategies including the use of small molecules to disrupt the protein-protein interaction or inhibit TEAD's auto-palmitoylation (PMID: 33571116). Current clinical candidates like IK-930 and IAG933 are being evaluated for their ability to suppress YAP-driven transcriptional programs in solid tumors (NCT05228015, NCT04857372). Beyond oncology, the complex is also implicated in fibrotic diseases, where it drives the activation of myofibroblasts. However, therapeutic inhibition must be carefully managed due to the complex's essential role in normal tissue regeneration and wound healing.

Other names

YAP1–TEAD complexYAP/TAZ–TEAD complexHippo pathway effector complexYAP–TEAD1/2/3/4 complex

Inhibition of the protein-protein interaction between YAP/TAZ and TEAD transcription factors, or covalent/non-covalent inhibition of the TEAD palmitoylation pocket to prevent transcriptional activity (PMID: 32814830, 33571116).