What is the Hippo pathway? Is the Hippo pathway conserved in Caenorhabditis elegans?

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The Hippo pathway was originally identified in Drosophila as the signalling pathway that governs organ size. The core of the pathway harbours two protein kinases (Hippo and Warts). Hippo phosphorylates and activates Warts, which in turn phosphorylates and inactivates the transcriptional co-activator Yorkie. As Yorkie mediates cell cycle-promoting and anti-apoptotic gene transcriptions, the Hippo pathway suppresses cell cycle progression and induces apoptosis. The pathway was named after Hippo, which was regarded as a key component. The pathway was initially considered to be well conserved in mammals. Indeed the mammalian homologues of Hippo, and Warts negatively regulate Yorkie homologue and function as the tumour suppressors. However, the researchers have identified numerous additional components both in Drosophila and mammals and the significant interspecies diversity is now evident. To make things more complicated, the regulation of the pathway does not necessarily depend on Hippo homologues. In this commentary, we reconsider what is essential for the Hippo pathway and try to sort out the controversial arguments in the discussion of the evolutionary root of the pathway.

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