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Systematic analysis of the Hippo pathway organization and oncogenic alteration in evolution.
The 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
De novo transcriptome sequencing and comprehensive analysis of the drought-responsive genes in the desert plant Cynanchum komarovii
The figure of an agarose gel with PCR products. (TIFF 11899 kb
Business scenarios, technical challenges and system requirements - D2.1
Deliverable D2.1 del projecte Europeu OneFIT (ICT-2009-257385)Preprin
Reactive oxygen-related diseases: therapeutic targets and emerging clinical indications
SIGNIFICANCE
Enhanced levels of reactive oxygen species (ROS) have been associated with different disease states. Most attempts to validate and exploit these associations by chronic antioxidant therapies have provided disappointing results. Hence, the clinical relevance of ROS is still largely unclear.
RECENT ADVANCES
We are now beginning to understand the reasons for these failures, which reside in the many important physiological roles of ROS in cell signaling. To exploit ROS therapeutically, it would be essential to define and treat the disease-relevant ROS at the right moment and leave physiological ROS formation intact. This breakthrough seems now within reach.
CRITICAL ISSUES
Rather than antioxidants, a new generation of protein targets for classical pharmacological agents includes ROS-forming or toxifying enzymes or proteins that are oxidatively damaged and can be functionally repaired.
FUTURE DIRECTIONS
Linking these target proteins in future to specific disease states and providing in each case proof of principle will be essential for translating the oxidative stress concept into the clinic. Antioxid. Redox Signal. 23, 1171-1185
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