Yes-associated protein–transcriptional coactivator with PDZ-binding motif–transcriptional enhancer factor domain protein protein-protein interaction (YAP/TAZ–TEAD PPI)

The YAP/TAZ–TEAD protein–protein interaction is a central node in the Hippo pathway, where the transcriptional coactivators Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) interact with the transcription factor family TEAD (TEAD1–4), orchestrating the expression of genes driving cell growth, survival, and tissue regeneration. Nuclear YAP/TAZ coactivate TEADs to stimulate transcription of pro-proliferative and anti-apoptotic target genes, and their aberrant activation is strongly implicated in tumorigenesis, therapy resistance, and organ overgrowth. Therapeutic targeting of the YAP/TAZ–TEAD interface (PPI) disrupts these transcriptional outputs, representing a promising anti-cancer strategy, though with accompanying risks due to the role of YAP/TAZ–TEAD in normal physiology. Drugs and peptides that disrupt this axis are under preclinical and investigational evaluation.

Other names

YAP–TEAD interactionTAZ–TEAD interactionYAP/TAZ–TEAD complexHippo pathway downstream PPI

Inhibitors disrupt YAP/TAZ–TEAD binding, blocking transcription of growth-promoting and anti-apoptotic genes. Peptides/small molecules may selectively impair YAP/TAZ transactivation domain binding to mediator components and TEAD, thus suppressing tumor growth and sensitizing to immunotherapy.