Hippo / YAP-TAZ pathway

The Hippo pathway is a conserved kinase cascade — centred on MST1/2 and LATS1/2 kinases — that controls organ size, tissue homeostasis, and stem cell activity by phosphorylating and thereby inactivating the transcriptional co-activators YAP (Yes-associated protein) and TAZ (transcriptional co-activator with PDZ-binding motif). When Hippo signalling is active, phosphorylated YAP/TAZ are sequestered in the cytoplasm or degraded; when the pathway is off, YAP/TAZ translocate to the nucleus, associate with TEAD transcription factors, and drive pro-proliferative and anti-apoptotic gene programmes. Mechanical cues, cell density, extracellular matrix stiffness, and G-protein-coupled receptor signals converge on the pathway. In ageing, increased tissue stiffness and altered mechanical environments can dysregulate YAP/TAZ, contributing to impaired regeneration and fibrosis; YAP/TAZ are also implicated in the SASP and senescence-bypass phenotypes.