The Experts below are selected from a list of 303 Experts worldwide ranked by ideXlab platform
Andrei V. Budanov - One of the best experts on this subject based on the ideXlab platform.
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Sensing the Environment Through Sestrins: Implications for Cellular Metabolism
International Review of Cell and Molecular Biology, 2016Co-Authors: Andrea Parmigiani, Andrei V. BudanovAbstract:Sestrins are a family of stress-responsive genes that have evolved to attenuate damage induced by stress caused to the cell. By virtue of their antioxidant activity, protein products of Sestrin genes prevent the accumulation of reactive oxygen species within the cell, thereby attenuating the detrimental effects of oxidative stress. In parallel, Sestrins participate in several signaling pathways that control the activity of the target of rapamycin protein kinase (TOR). TOR is a crucial sensor of intraCellular and extraCellular conditions that promotes cell growth and anabolism when nutrients and growth factors are abundant. In addition to reacting to stress-inducing insults, Sestrins also monitor the changes in the availability of nutrients, which allows them to serve as a key checkpoint for the TOR-regulated signaling pathways. In this review, we will discuss how Sestrins integrate signals from numerous stress- and nutrient-responsive signaling pathways to orchestrate Cellular Metabolism and support cell viability.
Andrea Parmigiani - One of the best experts on this subject based on the ideXlab platform.
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Sensing the Environment Through Sestrins: Implications for Cellular Metabolism
International Review of Cell and Molecular Biology, 2016Co-Authors: Andrea Parmigiani, Andrei V. BudanovAbstract:Sestrins are a family of stress-responsive genes that have evolved to attenuate damage induced by stress caused to the cell. By virtue of their antioxidant activity, protein products of Sestrin genes prevent the accumulation of reactive oxygen species within the cell, thereby attenuating the detrimental effects of oxidative stress. In parallel, Sestrins participate in several signaling pathways that control the activity of the target of rapamycin protein kinase (TOR). TOR is a crucial sensor of intraCellular and extraCellular conditions that promotes cell growth and anabolism when nutrients and growth factors are abundant. In addition to reacting to stress-inducing insults, Sestrins also monitor the changes in the availability of nutrients, which allows them to serve as a key checkpoint for the TOR-regulated signaling pathways. In this review, we will discuss how Sestrins integrate signals from numerous stress- and nutrient-responsive signaling pathways to orchestrate Cellular Metabolism and support cell viability.
Tamaki Suganuma - One of the best experts on this subject based on the ideXlab platform.
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serine and sam responsive complex sesame regulates histone modification crosstalk by sensing Cellular Metabolism
Molecular Cell, 2015Co-Authors: Shanshan Li, Selene K Swanson, Madelaine Gogol, Laurence Florens, Michael P Washburn, Jerry L Workman, Tamaki SuganumaAbstract:Pyruvate kinase M2 (PKM2) is a key enzyme for glycolysis and catalyzes the conversion of phosphoenolpyruvate (PEP) to pyruvate, which supplies Cellular energy. PKM2 also phosphorylates histone H3 threonine 11 (H3T11); however, it is largely unknown how PKM2 links Cellular Metabolism to chromatin regulation. Here, we show that the yeast PKM2 homolog, Pyk1, is a part of a novel protein complex named SESAME (Serine-responsive SAM-containing Metabolic Enzyme complex), which contains serine metabolic enzymes, SAM (S-adenosylmethionine) synthetases, and an acetyl-CoA synthetase. SESAME interacts with the Set1 H3K4 methyltransferase complex, which requires SAM synthesized from SESAME, and recruits SESAME to target genes, resulting in phosphorylation of H3T11. SESAME regulates the crosstalk between H3K4 methylation and H3T11 phosphorylation by sensing glycolysis and glucose-derived serine Metabolism. This leads to auto-regulation of PYK1 expression. Thus, our study provides insights into the mechanism of regulating gene expression, responding to Cellular Metabolism via chromatin modifications.
Michael P Washburn - One of the best experts on this subject based on the ideXlab platform.
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serine and sam responsive complex sesame regulates histone modification crosstalk by sensing Cellular Metabolism
Molecular Cell, 2015Co-Authors: Shanshan Li, Selene K Swanson, Madelaine Gogol, Laurence Florens, Michael P Washburn, Jerry L Workman, Tamaki SuganumaAbstract:Pyruvate kinase M2 (PKM2) is a key enzyme for glycolysis and catalyzes the conversion of phosphoenolpyruvate (PEP) to pyruvate, which supplies Cellular energy. PKM2 also phosphorylates histone H3 threonine 11 (H3T11); however, it is largely unknown how PKM2 links Cellular Metabolism to chromatin regulation. Here, we show that the yeast PKM2 homolog, Pyk1, is a part of a novel protein complex named SESAME (Serine-responsive SAM-containing Metabolic Enzyme complex), which contains serine metabolic enzymes, SAM (S-adenosylmethionine) synthetases, and an acetyl-CoA synthetase. SESAME interacts with the Set1 H3K4 methyltransferase complex, which requires SAM synthesized from SESAME, and recruits SESAME to target genes, resulting in phosphorylation of H3T11. SESAME regulates the crosstalk between H3K4 methylation and H3T11 phosphorylation by sensing glycolysis and glucose-derived serine Metabolism. This leads to auto-regulation of PYK1 expression. Thus, our study provides insights into the mechanism of regulating gene expression, responding to Cellular Metabolism via chromatin modifications.
Henan Xu - One of the best experts on this subject based on the ideXlab platform.
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n6 methyladenosine rna modification mediated Cellular Metabolism rewiring inhibits viral replication
Science, 2019Co-Authors: Zhike Lu, Jiang Yang, Panpan Li, Henan XuAbstract:Host cell Metabolism can be modulated by viral infection, affecting viral survival or clearance. Yet the Cellular Metabolism rewiring mediated by the N6-methyladenosine (m6A) modification in interactions between virus and host remains largely unknown. Here we report that in response to viral infection, host cells impair the enzymatic activity of the RNA m6A demethylase ALKBH5. This behavior increases the m6A methylation on α-ketoglutarate dehydrogenase (OGDH) messenger RNA (mRNA) to reduce its mRNA stability and protein expression. Reduced OGDH decreases the production of the metabolite itaconate that is required for viral replication. With reduced OGDH and itaconate production in vivo, Alkbh5-deficient mice display innate immune response–independent resistance to viral exposure. Our findings reveal that m6A RNA modification–mediated down-regulation of the OGDH-itaconate pathway reprograms Cellular Metabolism to inhibit viral replication, proposing potential targets for controlling viral infection.
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N6-methyladenosine RNA modification–mediated Cellular Metabolism rewiring inhibits viral replication
Science, 2019Co-Authors: Zhike Lu, Jiang Yang, Panpan Li, Henan XuAbstract:Host cell Metabolism can be modulated by viral infection, affecting viral survival or clearance. Yet the Cellular Metabolism rewiring mediated by the N6-methyladenosine (m6A) modification in interactions between virus and host remains largely unknown. Here we report that in response to viral infection, host cells impair the enzymatic activity of the RNA m6A demethylase ALKBH5. This behavior increases the m6A methylation on α-ketoglutarate dehydrogenase (OGDH) messenger RNA (mRNA) to reduce its mRNA stability and protein expression. Reduced OGDH decreases the production of the metabolite itaconate that is required for viral replication. With reduced OGDH and itaconate production in vivo, Alkbh5-deficient mice display innate immune response–independent resistance to viral exposure. Our findings reveal that m6A RNA modification–mediated down-regulation of the OGDH-itaconate pathway reprograms Cellular Metabolism to inhibit viral replication, proposing potential targets for controlling viral infection.