The Experts below are selected from a list of 318 Experts worldwide ranked by ideXlab platform
Peter Sarnow - One of the best experts on this subject based on the ideXlab platform.
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Viral inteRNAl Ribosome entry site elements: novel Ribosome-RNA complexes and roles in viral pathogenesis.
Journal of virology, 2003Co-Authors: Peter SarnowAbstract:Viruses have multifaceted approaches to ensure that viral genome amplification can be achieved in an efficient and, in some instances, a cell-type-specific manner. To accomplish this task, some viruses encode their own polymerases which selectively amplify the viral genomes; other viruses have evolved a variety of ways to compete directly with the host cell for factors that are needed for viral gene replication and packaging (5). However, there is one piece of macromolecular machinery in the host cell for which all viruses have to compete: the Ribosome. Early in infection, the viral mRNAs have to compete with the host, not so much for Ribosomes, but for the limited pool of eukaryotic initiation factors (eIFs) that mediate the recruitment of Ribosomes to both viral and cellular mRNAs (10). To circumvent this competition, viruses often modify certain eIFs within infected cells so that Ribosomes can be recruited selectively to viral mRNAs even though only a limited repertoire of eIFs is present (2). Of course, this strategy implies that such viral mRNAs have structural features that are distinct from most polymerase II-derived host mRNAs. For example, it was a long-standing puzzle how poliovirus, a human picoRNAvirus, can inhibit the translation of capped host cell mRNAs when translation of its own uncapped mRNA remained uninhibited. More than a decade ago, it was discovered that poliovirus, and all other picoRNAviruses, contain inteRNAl Ribosome entry site elements, commonly abbreviated as IRES elements, in their 5′ noncoding regions that can directly recruit ribosomal 40S subunits with a reduced set of eIFs (13, 24). The cap binding protein eIF-4E is especially dispensable for IRES activity in most viral IRES-containing mRNAs. Since then, IRES elements have been detected in many positive-stranded viral RNA genomes (9). More recently, IRESs have also been identified in Kaposi's sarcoma-associated herpesvirus, which contains a DNA genome. Specifically, a polycistronic transcript, found in all latently infected cells, is used to express the v-FLIP (FLICE-inhibitory protein) protein whose function is to counteract fatty acid synthase-induced apoptosis (1, 7). These findings have provided ample evidence that IRES elements have important functions in the viral life cycle, mostly to ensure efficient viral translation when components of the host translation machinery are limited due to virus-induced modification or host-induced antiviral responses, such as the phosphorylation of eIF-2 (9). In this minireview, I will discuss the surprising structural information we have obtained from studies on binary hepatitis C virus (HCV) IRES-40S complexes and the roles of specific canonical initiation and IRES-transacting factors (ITAFs) in translation initiation and in viral pathogenesis. I apologize for not mentioning and citing the many important contributions of other investigators who have made contributions in the viral IRES field. Due to space constraints in this minireview, I needed to focus on a few selected topics.
Chao H Lee - One of the best experts on this subject based on the ideXlab platform.
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EVALUATION OF THE POLYMERASE CHAIN REACTIONS FOR DETECTING THE ADHESIN GENE, SPECIES-SPECIFIC ANTIGEN, 16S Ribosome RNA GENE, UREASE A GENE, AND UREASE C GENE OF HELICOBACTER PYLORI IN GASTRIC BIOPSY SAMPLES. 687
Pediatric Research, 1996Co-Authors: Sonny K. F. Chong, Jinghong Wang, Qinyuan Lou, Joseph F. Fitzgerald, Chao H LeeAbstract:EVALUATION OF THE POLYMERASE CHAIN REACTIONS FOR DETECTING THE ADHESIN GENE, SPECIES-SPECIFIC ANTIGEN, 16S Ribosome RNA GENE, UREASE A GENE, AND UREASE C GENE OF HELICOBACTER PYLORI IN GASTRIC BIOPSY SAMPLES. 687
Seth J Weir - One of the best experts on this subject based on the ideXlab platform.
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gain of function genetic screen of the kinome reveals brsk2 as an inhibitor of the nrf2 transcription factor
Journal of Cell Science, 2020Co-Authors: Tigist Y Tamir, Brittany M Bowman, Megan J Agajanian, Dennis Goldfarb, Travis P Schrank, Trent Stohrer, Andrew E Hale, Priscila F Siesser, Seth J WeirAbstract:NFE2L2/NRF2 is a transcription factor and master regulator of cellular antioxidant response. Aberrantly high NRF2-dependent transcription is recurrent in human cancer, and conversely NRF2 activity is diminished with age and in neurodegenerative as well as metabolic disorders. Though NRF2 activating drugs are clinically beneficial, NRF2 inhibitors do not yet exist. Here we used a gain-of-function genetic screen of the kinome to identify new druggable regulators of NRF2 signaling. We found that the understudied protein kinase Brain Specific Kinase 2 (BRSK2) and the related BRSK1 kinases suppress NRF2-dependent transcription and NRF2 protein levels in an activity-dependent manner. Integrated phosphoproteomics and RNAseq studies revealed that BRSK2 drives AMPK signaling and suppresses the mTOR pathway. As a result, BRSK2 kinase activation suppressed Ribosome-RNA complexes, global protein synthesis, and NRF2 protein levels. Collectively our data illuminate the BRSK2 and BRSK1 kinases, in part by functionally connecting them to NRF2 signaling and mTOR. This signaling axis may prove useful for therapeutically targeting NRF2 in human disease.
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gain of function genetic screen of the kinome reveals brsk2 as an inhibitor of the nrf2 transcription factor
Journal of Cell Science, 2020Co-Authors: Tigist Y Tamir, Brittany M Bowman, Megan J Agajanian, Dennis Goldfarb, Travis P Schrank, Trent Stohrer, Andrew E Hale, Priscila F Siesser, Seth J WeirAbstract:NFE2L2/NRF2 is a transcription factor and master regulator of cellular antioxidant response. Aberrantly high NRF2-dependent transcription is recurrent in human cancer, and conversely NRF2 activity is diminished with age and in neurodegenerative as well as metabolic disorders. Though NRF2 activating drugs are clinically beneficial, NRF2 inhibitors do not yet exist. Here we used a gain-of-function genetic screen of the kinome to identify new druggable regulators of NRF2 signaling. We found that the understudied protein kinase Brain Specific Kinase 2 (BRSK2) and the related BRSK1 kinases suppress NRF2-dependent transcription and NRF2 protein levels in an activity-dependent manner. Integrated phosphoproteomics and RNAseq studies revealed that BRSK2 drives AMPK signaling and suppresses the mTOR pathway. As a result, BRSK2 kinase activation suppressed Ribosome-RNA complexes, global protein synthesis, and NRF2 protein levels. Collectively our data illuminate the BRSK2 and BRSK1 kinases, in part by functionally connecting them to NRF2 signaling and mTOR. This signaling axis may prove useful for therapeutically targeting NRF2 in human disease.
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gain of function genetic screen of the kinome reveals brsk2 as an inhibitor of the nrf2 transcription factor
bioRxiv, 2019Co-Authors: Tigist Y Tamir, Brittany M Bowman, Megan J Agajanian, Dennis Goldfarb, Travis P Schrank, Trent Stohrer, Andrew E Hale, Priscila F Siesser, Seth J Weir, Ryan C MurphyAbstract:NFE2L2/NRF2 is a transcription factor and master regulator of cellular antioxidant response. Aberrantly high NRF2-dependent transcription is recurrent in human cancer, and conversely NRF2 protein levels as well as activity is diminished with age and in neurodegenerative disorders. Though NRF2 activating drugs are clinically beneficial, NRF2 inhibitors do not yet exist. Here we used a gain-of-function genetic screen of the kinome to identify new druggable regulators of NRF2 signaling. We found that the understudied protein kinase Brain Specific Kinase 2 (BRSK2) and the related BRSK1 kinases suppress NRF2-dependent transcription and NRF2 protein levels in an activity-dependent manner. Integrated phosphoproteomics and RNAseq studies revealed that BRSK2 drives AMPK activation and suppresses mTOR signaling. As a result, BRSK2 kinase activation suppressed Ribosome-RNA complexes, global protein synthesis, and NRF2 protein levels. Collectively, our data establish the catalytically active BRSK2 kinase as a negative regulator of NRF2 via the AMPK/mTOR signaling. This signaling axis may prove useful for therapeutically targeting NRF2 in human diseases.
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gain of function genetic screen of the kinome reveals brsk2 as an inhibitor of the nrf2 transcription factor
bioRxiv, 2019Co-Authors: Tigist Y Tamir, Brittany M Bowman, Megan J Agajanian, Dennis Goldfarb, Travis P Schrank, Trent Stohrer, Andrew E Hale, Priscila F Siesser, Seth J Weir, Ryan M MurphyAbstract:NFE2L2/NRF2 is a transcription factor and master regulator of cellular antioxidant response. Aberrantly high NRF2-dependent transcription is recurrent in human cancer, and conversely NRF2 protein levels as well as activity is diminished with age and in neurodegenerative disorders. Though NRF2 activating drugs are clinically beneficial, NRF2 inhibitors do not yet exist. Here we used a gain-of-function genetic screen of the kinome to identify new druggable regulators of NRF2 signaling. We found that the understudied protein kinase Brain Specific Kinase 2 (BRSK2) and the related BRSK1 kinases suppress NRF2-dependent transcription and NRF2 protein levels in an activity-dependent manner. Integrated phosphoproteomics and RNAseq studies revealed that BRSK2 drives AMPK activation and suppresses mTOR signaling. As a result, BRSK2 kinase activation suppressed Ribosome-RNA complexes, global protein synthesis, and NRF2 protein levels. Collectively, our data establish the catalytically active BRSK2 kinase as a negative regulator of NRF2 via the AMPK/mTOR signaling. This signaling axis may prove useful for therapeutically targeting NRF2 in human diseases.
Dennis Goldfarb - One of the best experts on this subject based on the ideXlab platform.
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gain of function genetic screen of the kinome reveals brsk2 as an inhibitor of the nrf2 transcription factor
Journal of Cell Science, 2020Co-Authors: Tigist Y Tamir, Brittany M Bowman, Megan J Agajanian, Dennis Goldfarb, Travis P Schrank, Trent Stohrer, Andrew E Hale, Priscila F Siesser, Seth J WeirAbstract:NFE2L2/NRF2 is a transcription factor and master regulator of cellular antioxidant response. Aberrantly high NRF2-dependent transcription is recurrent in human cancer, and conversely NRF2 activity is diminished with age and in neurodegenerative as well as metabolic disorders. Though NRF2 activating drugs are clinically beneficial, NRF2 inhibitors do not yet exist. Here we used a gain-of-function genetic screen of the kinome to identify new druggable regulators of NRF2 signaling. We found that the understudied protein kinase Brain Specific Kinase 2 (BRSK2) and the related BRSK1 kinases suppress NRF2-dependent transcription and NRF2 protein levels in an activity-dependent manner. Integrated phosphoproteomics and RNAseq studies revealed that BRSK2 drives AMPK signaling and suppresses the mTOR pathway. As a result, BRSK2 kinase activation suppressed Ribosome-RNA complexes, global protein synthesis, and NRF2 protein levels. Collectively our data illuminate the BRSK2 and BRSK1 kinases, in part by functionally connecting them to NRF2 signaling and mTOR. This signaling axis may prove useful for therapeutically targeting NRF2 in human disease.
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gain of function genetic screen of the kinome reveals brsk2 as an inhibitor of the nrf2 transcription factor
Journal of Cell Science, 2020Co-Authors: Tigist Y Tamir, Brittany M Bowman, Megan J Agajanian, Dennis Goldfarb, Travis P Schrank, Trent Stohrer, Andrew E Hale, Priscila F Siesser, Seth J WeirAbstract:NFE2L2/NRF2 is a transcription factor and master regulator of cellular antioxidant response. Aberrantly high NRF2-dependent transcription is recurrent in human cancer, and conversely NRF2 activity is diminished with age and in neurodegenerative as well as metabolic disorders. Though NRF2 activating drugs are clinically beneficial, NRF2 inhibitors do not yet exist. Here we used a gain-of-function genetic screen of the kinome to identify new druggable regulators of NRF2 signaling. We found that the understudied protein kinase Brain Specific Kinase 2 (BRSK2) and the related BRSK1 kinases suppress NRF2-dependent transcription and NRF2 protein levels in an activity-dependent manner. Integrated phosphoproteomics and RNAseq studies revealed that BRSK2 drives AMPK signaling and suppresses the mTOR pathway. As a result, BRSK2 kinase activation suppressed Ribosome-RNA complexes, global protein synthesis, and NRF2 protein levels. Collectively our data illuminate the BRSK2 and BRSK1 kinases, in part by functionally connecting them to NRF2 signaling and mTOR. This signaling axis may prove useful for therapeutically targeting NRF2 in human disease.
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gain of function genetic screen of the kinome reveals brsk2 as an inhibitor of the nrf2 transcription factor
bioRxiv, 2019Co-Authors: Tigist Y Tamir, Brittany M Bowman, Megan J Agajanian, Dennis Goldfarb, Travis P Schrank, Trent Stohrer, Andrew E Hale, Priscila F Siesser, Seth J Weir, Ryan C MurphyAbstract:NFE2L2/NRF2 is a transcription factor and master regulator of cellular antioxidant response. Aberrantly high NRF2-dependent transcription is recurrent in human cancer, and conversely NRF2 protein levels as well as activity is diminished with age and in neurodegenerative disorders. Though NRF2 activating drugs are clinically beneficial, NRF2 inhibitors do not yet exist. Here we used a gain-of-function genetic screen of the kinome to identify new druggable regulators of NRF2 signaling. We found that the understudied protein kinase Brain Specific Kinase 2 (BRSK2) and the related BRSK1 kinases suppress NRF2-dependent transcription and NRF2 protein levels in an activity-dependent manner. Integrated phosphoproteomics and RNAseq studies revealed that BRSK2 drives AMPK activation and suppresses mTOR signaling. As a result, BRSK2 kinase activation suppressed Ribosome-RNA complexes, global protein synthesis, and NRF2 protein levels. Collectively, our data establish the catalytically active BRSK2 kinase as a negative regulator of NRF2 via the AMPK/mTOR signaling. This signaling axis may prove useful for therapeutically targeting NRF2 in human diseases.
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gain of function genetic screen of the kinome reveals brsk2 as an inhibitor of the nrf2 transcription factor
bioRxiv, 2019Co-Authors: Tigist Y Tamir, Brittany M Bowman, Megan J Agajanian, Dennis Goldfarb, Travis P Schrank, Trent Stohrer, Andrew E Hale, Priscila F Siesser, Seth J Weir, Ryan M MurphyAbstract:NFE2L2/NRF2 is a transcription factor and master regulator of cellular antioxidant response. Aberrantly high NRF2-dependent transcription is recurrent in human cancer, and conversely NRF2 protein levels as well as activity is diminished with age and in neurodegenerative disorders. Though NRF2 activating drugs are clinically beneficial, NRF2 inhibitors do not yet exist. Here we used a gain-of-function genetic screen of the kinome to identify new druggable regulators of NRF2 signaling. We found that the understudied protein kinase Brain Specific Kinase 2 (BRSK2) and the related BRSK1 kinases suppress NRF2-dependent transcription and NRF2 protein levels in an activity-dependent manner. Integrated phosphoproteomics and RNAseq studies revealed that BRSK2 drives AMPK activation and suppresses mTOR signaling. As a result, BRSK2 kinase activation suppressed Ribosome-RNA complexes, global protein synthesis, and NRF2 protein levels. Collectively, our data establish the catalytically active BRSK2 kinase as a negative regulator of NRF2 via the AMPK/mTOR signaling. This signaling axis may prove useful for therapeutically targeting NRF2 in human diseases.
Ryuji Kawaguchi - One of the best experts on this subject based on the ideXlab platform.
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Detection and identification of Escherichia coli, Shigella, and Salmonella by microarrays using the gyrB gene.
Biotechnology and Bioengineering, 2003Co-Authors: Kenichi Kakinuma, Masao Fukushima, Ryuji KawaguchiAbstract:Commonly, 16S Ribosome RNA (16S rRNA) sequence analysis has been used for identifying enteric bacteria. However, it may not always be applicable for distinguishing closely related bacteria. Therefore, we selected gyrB genes that encode the subunit B protein of DNA gyrase (a topoisomerase type II protein) as target genes. The molecular evolution rate of gyrB genes is higher than that of 16S rRNA, and gyrB genes are distributed universally among bacterial species. Microarray technology includes the methods of arraying cDNA or oligonucleotides on substrates such as glass slides while acquiring a lot of information simultaneously. Thus, it is possible to identify the enteric bacteria easily using microarray technology. We devised a simple method of rapidly identifying bacterial species through the combined use of gyrB genes and microarrays. Closely related bacteria were not identified at the species level using 16S rRNA sequence analysis, whereas they were identified at the species level based on the reaction patterns of oligonucleotides on our microarrays using gyrB genes. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 83: 721–728, 2003.
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Detection and identification of Escherichia coli, Shigella, and Salmonella by microarrays using the gyrB gene.
Biotechnology and bioengineering, 2003Co-Authors: Kenichi Kakinuma, Masao Fukushima, Ryuji KawaguchiAbstract:Commonly, 16S Ribosome RNA (16S rRNA) sequence analysis has been used for identifying enteric bacteria. However, it may not always be applicable for distinguishing closely related bacteria. Therefore, we selected gyrB genes that encode the subunit B protein of DNA gyrase (a topoisomerase type II protein) as target genes. The molecular evolution rate of gyrB genes is higher than that of 16S rRNA, and gyrB genes are distributed universally among bacterial species. Microarray technology includes the methods of arraying cDNA or oligonucleotides on substrates such as glass slides while acquiring a lot of information simultaneously. Thus, it is possible to identify the enteric bacteria easily using microarray technology. We devised a simple method of rapidly identifying bacterial species through the combined use of gyrB genes and microarrays. Closely related bacteria were not identified at the species level using 16S rRNA sequence analysis, whereas they were identified at the species level based on the reaction patterns of oligonucleotides on our microarrays using gyrB genes.
