YAP1 (YAP)
YAP1 (Yes-associated protein 1) is a transcriptional coactivator of the Hippo pathway, the pathway that responds to cell density and mechanical stretch.
Function
The Hippo pathway is a density sensor: when a tissue is crowded, MST1/2 and LATS1/2 kinases are active, and LATS phosphorylates YAP, which is then retained in the cytoplasm and degraded. When a cell has room - or is stretched by a stiff matrix, or loses cell-cell contact - Hippo signaling decreases, YAP dephosphorylates and enters the nucleus, and partners with TEAD transcription factors to drive genes for proliferation, survival, and extracellular-matrix remodeling. YAP therefore mediates the effect of tissue mechanics on gene expression.
In cancer
YAP1 amplification occurs in hepatocellular carcinoma, esophageal cancer, and others, and nuclear YAP is a marker of aggressive disease across tumor types. YAP drives the mechanotransduction that Mina Bissell’s tissue-architecture work predicted: stiff, remodeled matrix activates YAP, and YAP-activated cells remodel the matrix further. Its partner TAZ shares the function and the dysregulation. No direct YAP inhibitor is approved; drug development targets TEAD palmitoylation and YAP-TEAD binding.
Notes
- Human gene symbol: YAP1; UniProt P46937; 504 amino acids; TEAD-binding, PDZ-binding, WW domains.