Yes-associated protein 1 and Transcriptional coactivator with PDZ-binding motif (YAP1/TAZ)

Yes-associated protein 1 (YAP1) and Transcriptional coactivator with PDZ-binding motif (TAZ) are paralogous transcriptional coactivators that serve as the primary downstream effectors of the Hippo signaling pathway [1, 6]. They play a fundamental role in regulating organ size, cell proliferation, and tissue homeostasis by shuttling between the cytoplasm and the nucleus in response to mechanical and biochemical cues [13, 15]. In the nucleus, YAP1 and TAZ do not bind DNA directly but instead interact with TEA domain (TEAD) transcription factors to drive the expression of genes associated with cell survival, stemness, and epithelial-to-mesenchymal transition [3, 9]. Dysregulation of this pathway, leading to constitutive nuclear localization of YAP1/TAZ, is a hallmark of many solid tumors and is strongly associated with metastasis, chemoresistance, and poor clinical outcomes [4, 11]. Furthermore, YAP1/TAZ are key mediators of mechanotransduction, responding to extracellular matrix stiffness to promote fibrotic responses in organs such as the liver, lungs, and kidneys [12, 13]. Therapeutic development is currently focused on small molecules that disrupt the YAP/TAZ-TEAD interaction or inhibit TEAD palmitoylation, with several inhibitors currently in clinical and preclinical development for advanced cancers [2, 5].

Other names

Yes-associated protein 1 (YAP1)Transcriptional coactivator with PDZ-binding motif (TAZ)WW domain-containing transcription regulator 1 (WWTR1)YAPYAP65Hippo pathway effectors

Inhibition of the YAP/TAZ-TEAD transcriptional complex through direct disruption of protein-protein interactions, inhibition of TEAD auto-palmitoylation, or modulation of upstream Hippo pathway kinases [2, 3, 5].