title: Genome-wide screening for genes associated with valproic acid sensitivity in fission yeast.
abstract: We have been studying the action mechanisms of valproic acid (VPA) in fission yeast Schizosaccharomyces pombe by developing a genetic screen for mutants that show hypersensitivity to VPA. In the present study, we performed a genome-wide screen of 3004 haploid deletion strains and confirmed 148 deletion strains to be VPA sensitive. Of the 148 strains, 93 strains also showed sensitivity to another aliphatic acids HDAC inhibitor, sodium butyrate (SB), and 55 strains showed sensitivity to VPA but not to SB. Interestingly, we found that both VPA and SB treatment induced a marked increase in the transcription activity of Atf1 in wild-type cells. However, in clr6-1, a mutant allele the clr6(+) gene encoding class I HDAC, neither VPA- nor SB induced the activation of Atf1 transcription activity. We also found that VPA, but not SB, caused an increase in cytoplasmic Ca(2+) level. We further found that the cytoplasmic Ca(2+) increase was caused by Ca(2+) influx from extracellular medium via Cch1-Yam8 channel complex. Altogether, our present study indicates that VPA and SB play similar but distinct roles in multiple physiological processes in fission yeast.
authors.affiliation: Division of Molecular Pharmacology and Pharmacogenomics, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhang
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
authors.forename: Qingbin
authors.initials: Q
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
mesh_terms: D000107:Acetylation; D001692:Biological Transport / Q000187:drug effects; D020148:Butyric Acid / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D025141:Drug Resistance, Fungal / Q000235:genetics*; D005800:Genes, Fungal; D055106:Genome-Wide Association Study; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006657:Histones / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D009154:Mutation; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015533:Transcriptional Activation; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D015220:Calcium Channels; C568273:Cch1 protein, S pombe; D018797:Cell Cycle Proteins; C115303:Clr6 protein, S pombe; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D008562:Membrane Glycoproteins; D011506:Proteins; D029702:Schizosaccharomyces pombe Proteins; C405644:YAM8 protein, S pombe; D020148:Butyric Acid; D014635:Valproic Acid; C079238:alcohol O-acetyltransferase; D002118:Calcium