scholarly journals The Hippo pathway origin and its oncogenic alteration in evolution

2019 ◽  
Author(s):  
Yuxuan Chen ◽  
Han Han ◽  
Gayoung Seo ◽  
Rebecca Vargas ◽  
Bing Yang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Evolutionary History ◽  
Somatic Mutations ◽  
Hippo Pathway ◽  
Evolutionary Perspective ◽  
Paralogous Gene ◽  
Evolutionarily Conserved ◽  
History Of ◽  
Unicellular Origin ◽  
The Hippo Pathway

AbstractThe Hippo pathway is a central regulator of organ size and a key tumor suppressor via coordinating cell proliferation and death. Initially discovered in Drosophila, the Hippo pathway has been implicated as an evolutionarily conserved pathway in mammals; however, how this pathway was evolved to be functional from its origin is still largely unknown. In this study, we traced the Hippo pathway in premetazoan species, characterized the intrinsic functions of its ancestor components, and unveiled the evolutionary history of this key signaling pathway from its unicellular origin. In addition, we elucidated the paralogous gene history for the mammalian Hippo pathway components and characterized their cancer-derived somatic mutations from an evolutionary perspective. Taken together, our findings not only traced the conserved function of the Hippo pathway to its unicellular ancestor components, but also provided novel evolutionary insights into the Hippo pathway organization and oncogenic alteration.

scholarly journals NPHP4, a cilia-associated protein, negatively regulates the Hippo pathway

2011 ◽  
Vol 193 (4) ◽  
pp. 633-642 ◽  
Author(s):  
Sandra Habbig ◽  
Malte P. Bartram ◽  
Roman U. Müller ◽  
Ricarda Schwarz ◽  
Nikolaos Andriopoulos ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cellular Proliferation ◽  
Nuclear Translocation ◽  
Hippo Pathway ◽  
Negative Regulator ◽  
Hippo Signaling ◽  
Transcriptional Coactivator ◽  
Hippo Signaling Pathway ◽  
The Hippo Pathway ◽  
Potent Negative Regulator

The conserved Hippo signaling pathway regulates organ size in Drosophila melanogaster and mammals and has an essential role in tumor suppression and the control of cell proliferation. Recent studies identified activators of Hippo signaling, but antagonists of the pathway have remained largely elusive. In this paper, we show that NPHP4, a known cilia-associated protein that is mutated in the severe degenerative renal disease nephronophthisis, acts as a potent negative regulator of mammalian Hippo signaling. NPHP4 directly interacted with the kinase Lats1 and inhibited Lats1-mediated phosphorylation of the Yes-associated protein (YAP) and TAZ (transcriptional coactivator with PDZ-binding domain), leading to derepression of these protooncogenic transcriptional regulators. Moreover, NPHP4 induced release from 14-3-3 binding and nuclear translocation of YAP and TAZ, promoting TEA domain (TEAD)/TAZ/YAP-dependent transcriptional activity. Consistent with these data, knockdown of NPHP4 negatively affected cellular proliferation and TEAD/TAZ activity, essentially phenocopying loss of TAZ function. These data identify NPHP4 as a negative regulator of the Hippo pathway and suggest that NPHP4 regulates cell proliferation through its effects on Hippo signaling.

scholarly journals Cross-Talk Between Mitochondrial Fusion and the Hippo Pathway in Controlling Cell Proliferation During Drosophila Development

Genetics ◽  
2016 ◽  
Vol 203 (4) ◽  
pp. 1777-1788 ◽  
Author(s):  
Qiannan Deng ◽  
Ting Guo ◽  
Xiu Zhou ◽  
Yongmei Xi ◽  
Xiaohang Yang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cross Talk ◽  
Hippo Pathway ◽  
Mitochondrial Fusion ◽  
Drosophila Development ◽  
The Hippo Pathway

One Hippo and many masters: differential regulation of the Hippo pathway in cancer

2014 ◽  
Vol 42 (4) ◽  
pp. 816-821 ◽  
Author(s):  
David Romano ◽  
David Matallanas ◽  
Dennie T. Frederick ◽  
Keith T. Flaherty ◽  
Walter Kolch
Keyword(s):  
Protein Interactions ◽  
Hippo Pathway ◽  
Promoter Hypermethylation ◽  
Protein Protein Interactions ◽  
Evolutionarily Conserved ◽  
Or Gene ◽  
Phosphoinositide 3 Kinase ◽  
Ras Isoforms ◽  
The Hippo Pathway

The Hippo/MST2 (mammalian sterile 20-like kinase 2) pathway is a signalling cascade evolutionarily conserved in its structure. Originally described in Drosophila melanogaster as a regulator of organ size, this pathway has greater functions in mammals. Disturbance of mammalian MST2 pathway is associated with tumorigenesis by affecting apoptosis, cell cycle and polarity. In addition, this pathway has been shown to cross-talk with mitogenic pathways at multiple levels. In the present mini-review, we discuss our contribution highlighting the regulation of MST2 signalling by frequently observed oncogenic perturbations affecting mitogenic pathways. In particular, we review the role of RAS isoforms and PI3K (phosphoinositide 3-kinase)/Akt in the regulation of MST2 activity by phosphorylation. We also put the emphasis on RAF-induced control of MST2 signalling by protein–protein interactions. Finally, we recapitulate some of the direct mechanisms, such as ubiquitin-dependent degradation or gene silencing by promoter hypermethylation, involved in MST2 pathway component down-regulation in cancers.

scholarly journals The Hippo pathway regulates intestinal stem cell proliferation during Drosophila adult midgut regeneration

Development ◽  
2010 ◽  
Vol 137 (24) ◽  
pp. 4147-4158 ◽  
Author(s):  
R. L. Shaw ◽  
A. Kohlmaier ◽  
C. Polesello ◽  
C. Veelken ◽  
B. A. Edgar ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Stem Cell ◽  
Hippo Pathway ◽  
Intestinal Stem Cell ◽  
Stem Cell Proliferation ◽  
The Hippo Pathway
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