Show simple item record

dc.contributor.authorNemoto, N
dc.contributor.authorUdagawa, T
dc.contributor.authorOhira, T
dc.contributor.authorJiang, L
dc.contributor.authorHirota, K
dc.contributor.authorWilkinson, Caroline R M
dc.contributor.authorBähler, J
dc.contributor.authorJones, Nic
dc.contributor.authorOhta, K
dc.contributor.authorWek, R
dc.contributor.authorAsano, K
dc.date.accessioned2011-01-24T11:27:12Z
dc.date.available2011-01-24T11:27:12Z
dc.date.issued2010-11-26
dc.identifier.citationThe roles of stress-activated Sty1 and Gcn2 kinases and of the protooncoprotein homologue Int6/eIF3e in responses to endogenous oxidative stress during histidine starvation. 2010, 404 (2):183-201 J Mol Biolen
dc.identifier.issn1089-8638
dc.identifier.pmid20875427
dc.identifier.doi10.1016/j.jmb.2010.09.016
dc.identifier.urihttp://hdl.handle.net/10541/120267
dc.description.abstractIn fission yeast, Sty1 and Gcn2 are important protein kinases that regulate gene expression in response to amino acid starvation. The translation factor subunit Int6/eIF3e promotes Sty1-dependent response by increasing the abundance of Atf1, a transcription factor targeted by Sty1. While Gcn2 promotes expression of amino acid biosynthesis enzymes, the mechanism and function of Sty1 activation and Int6/eIF3e involvement during this nutrient stress are not understood. Here we show that mutants lacking sty1(+) or gcn2(+) display reduced viabilities during histidine depletion stress in a manner suppressible by the antioxidant N-acetyl cysteine, suggesting that these protein kinases function to alleviate endogenous oxidative damage generated during nutrient starvation. Int6/eIF3e also promotes cell viability by a mechanism involving the stimulation of Sty1 response to oxidative damage. In further support of these observations, microarray data suggest that, during histidine starvation, int6Δ increases the duration of Sty1-activated gene expression linked to oxidative stress due to the initial attenuation of Sty1-dependent transcription. Moreover, loss of gcn2 induces the expression of a new set of genes not activated in wild-type cells starved for histidine. These genes encode heatshock proteins, redox enzymes, and proteins involved in mitochondrial maintenance, in agreement with the idea that oxidative stress is imposed on gcn2Δ cells. Furthermore, early Sty1 activation promotes rapid Gcn2 activation on histidine starvation. These results suggest that Gcn2, Sty1, and Int6/eIF3e are functionally integrated and cooperate to respond to oxidative stress generated during histidine starvation.
dc.language.isoenen
dc.subject.meshActivating Transcription Factor 1
dc.subject.meshAmitrole
dc.subject.meshBase Sequence
dc.subject.meshDNA, Fungal
dc.subject.meshEukaryotic Initiation Factor-3
dc.subject.meshFeedback, Physiological
dc.subject.meshGene Expression Regulation, Fungal
dc.subject.meshGenes, Fungal
dc.subject.meshHistidine
dc.subject.meshMAP Kinase Signaling System
dc.subject.meshMitogen-Activated Protein Kinases
dc.subject.meshModels, Biological
dc.subject.meshMutation
dc.subject.meshOxidative Stress
dc.subject.meshPhosphoproteins
dc.subject.meshProtein-Serine-Threonine Kinases
dc.subject.meshSchizosaccharomyces
dc.subject.meshSchizosaccharomyces pombe Proteins
dc.subject.meshTranscription, Genetic
dc.titleThe roles of stress-activated Sty1 and Gcn2 kinases and of the protooncoprotein homologue Int6/eIF3e in responses to endogenous oxidative stress during histidine starvation.en
dc.typeArticleen
dc.contributor.departmentMolecular, Cellular, and Developmental Biology Program, Division of Biology, Kansas State University, Manhattan, KS 66506, USA.en
dc.identifier.journalJournal of Molecular Biologyen
html.description.abstractIn fission yeast, Sty1 and Gcn2 are important protein kinases that regulate gene expression in response to amino acid starvation. The translation factor subunit Int6/eIF3e promotes Sty1-dependent response by increasing the abundance of Atf1, a transcription factor targeted by Sty1. While Gcn2 promotes expression of amino acid biosynthesis enzymes, the mechanism and function of Sty1 activation and Int6/eIF3e involvement during this nutrient stress are not understood. Here we show that mutants lacking sty1(+) or gcn2(+) display reduced viabilities during histidine depletion stress in a manner suppressible by the antioxidant N-acetyl cysteine, suggesting that these protein kinases function to alleviate endogenous oxidative damage generated during nutrient starvation. Int6/eIF3e also promotes cell viability by a mechanism involving the stimulation of Sty1 response to oxidative damage. In further support of these observations, microarray data suggest that, during histidine starvation, int6Δ increases the duration of Sty1-activated gene expression linked to oxidative stress due to the initial attenuation of Sty1-dependent transcription. Moreover, loss of gcn2 induces the expression of a new set of genes not activated in wild-type cells starved for histidine. These genes encode heatshock proteins, redox enzymes, and proteins involved in mitochondrial maintenance, in agreement with the idea that oxidative stress is imposed on gcn2Δ cells. Furthermore, early Sty1 activation promotes rapid Gcn2 activation on histidine starvation. These results suggest that Gcn2, Sty1, and Int6/eIF3e are functionally integrated and cooperate to respond to oxidative stress generated during histidine starvation.


Files in this item

This item appears in the following Collection(s)

Show simple item record