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Full-Text Articles in Life Sciences
Stress-Induced Alternative Splice Forms Of Mdm2 And Mdmx Modulate The P53-Pathway In Distinct Ways, Matthew F. Rouhier, Aishwarya G. Jacob, Ravi K. Singh, Daniel F. Comiskey Jr, Fuad Mohammad, Thomas W. Bebee, Dawn S. Chandler
Stress-Induced Alternative Splice Forms Of Mdm2 And Mdmx Modulate The P53-Pathway In Distinct Ways, Matthew F. Rouhier, Aishwarya G. Jacob, Ravi K. Singh, Daniel F. Comiskey Jr, Fuad Mohammad, Thomas W. Bebee, Dawn S. Chandler
Matthew F Rouhier
MDM2 and MDMX are the chief negative regulators of the tumor-suppressor protein p53 and are essential for maintaining homeostasis within the cell. In response to genotoxic stress and also in several cancer types, MDM2 and MDMX are alternatively spliced. The splice variants MDM2-ALT1 and MDMX-ALT2 lack the p53-binding domain and are incapable of negatively regulating p53. However, they retain the RING domain that facilitates dimerization of the full-length MDM proteins. Concordantly, MDM2-ALT1 has been shown to lead to the stabilization of p53 through its interaction with and inactivation of full-length MDM2. The impact of MDM2-ALT1 expression on the p53 pathway …
Pharmacological Validation Of An Inward-Rectifier Potassium (Kir) Channel As An Insecticide Target In The Yellow Fever Mosquito Aedes Aegypti, Matthew F. Rouhier, Rene Raphemot, Jerod S. Denton, Peter M. Piermarini
Pharmacological Validation Of An Inward-Rectifier Potassium (Kir) Channel As An Insecticide Target In The Yellow Fever Mosquito Aedes Aegypti, Matthew F. Rouhier, Rene Raphemot, Jerod S. Denton, Peter M. Piermarini
Matthew F Rouhier
Mosquitoes are important disease vectors that transmit a wide variety of pathogens to humans, including those that cause malaria and dengue fever. Insecticides have traditionally been deployed to control populations of disease-causing mosquitoes, but the emergence of insecticide resistance has severely limited the number of active compounds that are used against mosquitoes. Thus, to improve the control of resistant mosquitoes there is a need to identify new insecticide targets and active compounds for insecticide development. Recently we demonstrated that inward rectifier potassium (Kir) channels and small molecule inhibitors of Kir channels offer promising new molecular targets and active compounds, respectively, …
Discovery And Characterization Of A Potent And Selective Inhibitory Of Aedes Aegypti Inward Rectifier Potassium Channels, Matthew F. Rouhier, Rene Raphemot, Daniel R. Swale, Emily Days, C. David Weaver, Kimberly M. Lovell, Leah C. Konkel, Darren W. Engers, Sean F. Bollinger, Corey Hopkins, Peter M. Piermarini, Jerod S. Denton
Discovery And Characterization Of A Potent And Selective Inhibitory Of Aedes Aegypti Inward Rectifier Potassium Channels, Matthew F. Rouhier, Rene Raphemot, Daniel R. Swale, Emily Days, C. David Weaver, Kimberly M. Lovell, Leah C. Konkel, Darren W. Engers, Sean F. Bollinger, Corey Hopkins, Peter M. Piermarini, Jerod S. Denton
Matthew F Rouhier
Vector-borne diseases such as dengue fever and malaria, which are transmitted by infected female mosquitoes, affect nearly half of the world's population. The emergence of insecticide-resistant mosquito populations is reducing the effectiveness of conventional insecticides and threatening current vector control strategies, which has created an urgent need to identify new molecular targets against which novel classes of insecticides can be developed. We previously demonstrated that small molecule inhibitors of mammalian Kir channels represent promising chemicals for new mosquitocide development. In this study, high-throughput screening of approximately 30,000 chemically diverse small-molecules was employed to discover potent and selective inhibitors of Aedes …
Eliciting Renal Failure In Mosquitoes With A Small-Molecule Inhibitor Of Inward-Rectifying Potassium Channels, Matthew F. Rouhier, Rene Raphemot, Corey R. Hopkins, Rocco D. Gogliotti, Kimberly M. Lovel, Rebecca M. Hine, Dhairyasheel Ghosalkar, Anthony Longo, Klaus W. Beyenbach, Jerod S. Denton, Peter M. Piermarini
Eliciting Renal Failure In Mosquitoes With A Small-Molecule Inhibitor Of Inward-Rectifying Potassium Channels, Matthew F. Rouhier, Rene Raphemot, Corey R. Hopkins, Rocco D. Gogliotti, Kimberly M. Lovel, Rebecca M. Hine, Dhairyasheel Ghosalkar, Anthony Longo, Klaus W. Beyenbach, Jerod S. Denton, Peter M. Piermarini
Matthew F Rouhier
Mosquito-borne diseases such as malaria and dengue fever take a large toll on global health. The primary chemical agents used for controlling mosquitoes are insecticides that target the nervous system. However, the emergence of resistance in mosquito populations is reducing the efficacy of available insecticides. The development of new insecticides is therefore urgent. Here we show that VU573, a small-molecule inhibitor of mammalian inward-rectifying potassium (Kir) channels, inhibits a Kir channel cloned from the renal (Malpighian) tubules of Aedes aegypti (AeKir1). Injection of VU573 into the hemolymph of adult female mosquitoes (Ae. aegypti) disrupts the production and excretion of urine …