The Hippo signal is very conservative in evolution. It regulates organ size and tissue stability by regulating cell proliferation, apoptosis, and stem cell renewal. The core process of Hippo signaling is a kinase tandem process, Mst1/2 and Sav1 form a complex, phosphorylate and activate Lats1/2; Lats1/2 kinase then phosphorylates and inhibits transcriptional coactivators Yap and Taz. Yap and Taz are the most important effectors downstream of the Hippo pathway. Upon dephosphorylation, Yap and Taz translocate to the nucleus and interact with TEAD1-4 or other transcription factors (such as CTGF) to induce gene expression, thereby initiating cell proliferation and inhibiting apoptosis.Mst1/2 and LATS1/2 in the Hippo signaling pathway can be regulated by many molecules, including Merlin, KIBRA, RASSFs, RHO, Ajuba, 14-3-3, α-catenin, AMOT, F-actin, ITCH, MAP4K4/6 /7 and so on. In recent years, the interaction between Hippo signaling pathway and other fields or signaling pathways, such as cancer, immunity, epigenetics, GPCR, Wnt, Smad, mTOR, etc., is gaining unprecedented traction. The trend brings a new direction and challenges to the research of Hippo signaling pathway.
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