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Hippo

The Hippo signaling pathway, also known as the Salvador/Warts/Hippo pathway, has emerged recently as a growth control pathway. In a classical view, the core of the Hippo pathway in mammals is a kinase cascade in which the mammalian Ste20-like kinases 1/2 (MST1/2; homologs of Drosophila Hippo [Hpo]) phosphorylate and activate large tumor suppressor 1/2 (LATS1/2; homologs of Drosophila Warts [Wts]). The Hippo kinase cascade can be initiated by TAO kinases (TAOK1/2/3), which phosphorylate the activation loop of MST1/2 (Thr183 for MST1 and Thr180 for MST2; hereafter, all residues refer to human proteins) and thereby lead to MST1/2 activation. The transcriptional co-factors, yes-associated protein (YAP), and transcriptional co-activator with PDZ-binding motif (TAZ) together form the transcriptional module. YAP/TAZ bind to the transcription factor TEAD and upregulate genes important for proliferation and cell survival.Hippo signaling is an evolutionarily conserved pathway that controls organ size by regulating cell proliferation, apoptosis, and stem cell self-renewal. Dysregulation of this signaling pathway contributes toward cancer development.1.Meng Z,et al. Genes Dev. 2016 Jan 1;30(1):1-17.