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Review
. 2015 Apr;21(4):212-22.
doi: 10.1016/j.molmed.2015.01.003. Epub 2015 Feb 18.

Disease implications of the Hippo/YAP pathway

Steven W Plouffe  1 , Audrey W Hong  1 , Kun-Liang Guan  2
Affiliations
Review

Disease implications of the Hippo/YAP pathway

Steven W Plouffe et al. Trends Mol Med. 2015 Apr.

Abstract

The Hippo signaling pathway is important for controlling organ size and tissue homeostasis. Originally identified in Drosophila melanogaster, the core components of the Hippo pathway are highly conserved in mammals. The Hippo pathway can be modulated by a wide range of stimuli, including G protein-coupled receptor (GPCR) signaling, changes in the actin cytoskeleton, cell-cell contact, and cell polarity. When activated, the Hippo pathway functions as a tumor suppressor to limit cell growth. However, dysregulation by genetic inactivation of core pathway components or amplification or gene fusion of its downstream effectors results in increased cell proliferation and decreased apoptosis and differentiation. Unsurprisingly, this can lead to tissue overgrowth, tumorigenesis, and many other diseases.

Keywords: Hippo; TAZ; YAP; cancer; disease.

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Figures

Figure 1
Figure 1. The Hippo signaling pathway
When the Hippo pathway is activated, MST1/2 in complex with SAV1 phosphorylate and activate LATS1/2 and MOB1. When activated, LATS1/2 phosphorylates YAP/TAZ, the primary effectors of the Hippo pathway. When phosphorylated, YAP/TAZ are sequestered in the cytoplasm or degraded. When YAP/TAZ are dephosphorylated, they translocate to the nucleus where they interact with TEAD1-4 to induce transcription and promote cell proliferation and inhibit apoptosis. Arrows and blunt ends indicate activation and inhibition, respectively.
Figure 2
Figure 2. Disease implications of the Hippo pathway
Dysregulation of the Hippo pathway has been implicated in a number of cancers and diseases throughout the body. Dysregulation may be due to genetic inactivation of core pathway components or amplification or gene fusion of its downstream effectors YAP and TAZ. Here we briefly summarize some of the diseases covered in this review.
See this image and copyright information in PMC

References

    1. Callus BA, et al. Association of mammalian sterile twenty kinases, Mst1 and Mst2, with hSalvador via C-terminal coiled-coil domains, leads to its stabilization and phosphorylation. FEBS J. 2006;273:4264–4276. - PubMed
    1. Tapon N, et al. salvador Promotes Both Cell Cycle Exit and Apoptosis in Drosophila and Is Mutated in Human Cancer Cell Lines. Cell. 2002;110:467–478. - PubMed
    1. Chan EH, et al. The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1. Oncogene. 2005;24:2076–2086. - PubMed
    1. Praskova M, et al. MOBKL1A/MOBKL1B phosphorylation by MST1 and MST2 inhibits cell proliferation. Curr Biol. 2008;18:311–321. - PMC - PubMed
    1. Huang J, et al. The Hippo signaling pathway coordinately regulates cell proliferation and apoptosis by inactivating Yorkie, the Drosophila Homolog of YAP. Cell. 2005;122:421–434. - PubMed

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