First discovered in Drosophila, the Hippo pathway regulates the size and shape of organ development. Its discovery and study have helped to address longstanding questions in developmental biology. Central to this pathway is a kinase cascade leading from the tumor suppressor Hippo (Mst1 and Mst2 in mammals) to the Yki protein (YAP and TAZ in mammals), a transcriptional coactivator of target genes involved in cell proliferation, survival, and apoptosis. A dysfunction of the Hippo pathway activity is frequently detected in human cancers. Recent studies have highlighted that the Hippo pathway may play an important role in tissue homoeostasis through the regulation of stem cells, cell differentiation, and tissue regeneration. Recently, the impact of RASSF proteins on Hippo signaling potentiating its proapoptotic activity has been addressed, thus, providing further evidence for Hippo's key role in mammalian tumorigenesis as well as other important diseases. 1. Introduction The Hippo pathway is a signaling pathway that regulates cell growth and cell death. It was discovered in Drosophila melanogaster as a pathway controlling organ size and of which mutations lead to tumorigenesis. This pathway is highly conserved, and its activation or repression could lead to the following most extreme outcomes: proliferation/transformation and death/tumor suppression. The Hippo pathway cross-talks with other signaling players such as Notch, Wnt, and Sonic hedgehog (Shh). It influences several biological events, and its dysfunction may possibly lie behind many human cancers. In this review, we discuss the complex data reported about Drosophila to date (schematic representation in Figure 1) and the human Hippo (schematic representation in Figure 2) pathways focusing on the relationship between the tumor suppression rassf protein family and the Hippo-like pathway in humans [1, 2]. Figure 1: “Hpo signaling pathway in Drosophila.” Schematic representation of Hippo kinases cascade and of its modulation by apical transmenbrame protein complexes. Figure 2: “Hpo signaling pathway in Mammals and the cross-talk with RASFF1A signaling.” Schematic representation of mammalian Hippo kinases cascade and interconnections between Hippo pathway and rassf1a protein signal. Red lines indicate the impact of rassf1a signaling in modulating activity of Hpo pathway components. 2. The Hippo Signaling Network in Drosophila Drosophila imaginal discs have facilitated molecular dissecting of signaling pathways controlling organ size during development. These imaginal discs allow to screen how organs grow
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