Hippo signaling: To die or not to die

摘要

In this issue of CDD, Reuven et a} provide an elegant mechanism by which LATS2, a core component of the Hippo pathway, impedes DNA damage-induced apoptosis through inhibition of c-Abl. By dissecting signaling events upon nu-irradiation of sparse and dense cell, the authors revealed a dialogue between Hippo signaling members and DNA damage response (DDR) proteins. The mammalian Hippo tumor suppressor pathway has pivotal roles in regulating organ size, stem cell pluripotency and tumorigenesis. The Hippo pathway is composed of a kinase cascade core that includes the MST1/2 serine/threonine kinase, the WW45 scaffold protein, MOB, and the serine/threonine LATS1/2 kinase. Activation of the core cascade through, for example, cell-cell contact due to high cell density leads to phosphorylation of the YAP and TAZ oncoproteins, leading to their sequestration in the cytoplasm and preventing their binding to TEAD transcription factors. This inhibits transcription of downstream target genes implicated in proliferation, anti-apoptosis and epithelial-to-mesenchymal transition. Hippo signaling thus acts through this pathway to suppress tumorigenesis.