Yes-associated protein 1 (YAP1)

Yes-Associated Protein 1 (YAP1) is a transcriptional coactivator protein that serves as a principal effector of the Hippo signaling pathway. Lacking its own DNA-binding domain, YAP1 acts by partnering with sequence-specific transcription factors—most notably the TEAD family—to switch on gene expression programs governing cell proliferation, survival, tissue growth, and regeneration. Its activity is controlled by upstream Hippo kinases, which phosphorylate YAP1 to retain it in the cytoplasm; when this restraint weakens, YAP1 translocates to the nucleus, where it can also form biomolecular condensates that concentrate transcriptional machinery and interacting partners such as JUNB and TCF12. Because it integrates mechanical cues from the extracellular matrix and cytoskeleton with biochemical signals, YAP1 is a central node in mechanotransduction.

In biomedical research, YAP1 is studied chiefly as an oncogenic and pro-fibrotic signaling protein alongside its paralog WWTR1 (TAZ). Elevated or sustained YAP1 activity is linked to tumor progression, stemness, and therapy resistance across cancers including hepatocellular carcinoma, ovarian cancer, and small cell neuroendocrine carcinoma, and it intersects with pathways such as Phosphatidylinositol 3-kinase (PI3K)/Protein kinase B (PKB)/mTOR and MAPK signaling and with the tumor microenvironment. YAP1 also drives maladaptive tissue responses—for example, tubular cell cellular senescence and epithelial–mesenchymal transition in kidney fibrosis, and TGF-β–associated remodeling—while conversely supporting beneficial repair in wound healing and neuronal differentiation through mechanotransduction. Additional work connects YAP1 to ferroptosis regulation via axes involving Gpx4 and GLS1. These roles make YAP1 an actively pursued therapeutic target, addressed through approaches ranging from small-molecule inhibitors such as verteporfin to lipid nanoparticle–delivered siRNA that silences its expression.