The Hippo signaling pathway, also known as the Salvador/Warts/Hippo (SWH) pathway, plays an evolutionarily conserved fundamental role in controlling organ sizes in multicellular organisms through the regulation of cell proliferation and apoptosis. The pathway is regulated by various stimuli, such as G-protein coupled receptor signaling, cellular energy status, mechanical stress, etc. As shown in the figure, when activated, the Hippo kinase cascade phosphorylates and inhibits the transcription co-activator YAP (Yes-associated protein), and its paralog TAZ (transcriptional coactivator with PDZ-binding motif), resulting in their cytoplasmic retention and degradation. On the contrary, dephosphorylated YAP/TAZ translocates into the nucleus and activate gene transcription through binding to TEAD family and other transcription factors. Such changes in gene expression promote cell proliferation and stem cell/progenitor cell self-renewal but inhibit apoptosis, thereby coordinately promote increase in organ size, tissue regeneration, and tumorigenesis.
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