title: Sphingoid base is required for translation initiation during heat stress in Saccharomyces cerevisiae.
abstract: Sphingolipids are required for many cellular functions including response to heat shock. We analyzed the yeast lcb1-100 mutant, which is conditionally impaired in the first step of sphingolipid biosynthesis and shows a strong decrease in heat shock protein synthesis and viability. Transcription and nuclear export of heat shock protein mRNAs is not affected. However, lcb1-100 cells exhibited a strong decrease in protein synthesis caused by a defect in translation initiation under heat stress conditions. The essential lipid is sphingoid base, not ceramide or sphingoid base phosphates. Deletion of the eIF4E-binding protein Eap1p in lcb-100 cells restored translation of heat shock proteins and increased viability. The translation defect during heat stress in lcb1-100 was due at least partially to a reduced function of the sphingoid base-activated PKH1/2 protein kinases. In addition, depletion of the translation initiation factor eIF4G was observed in lcb1-100 cells and ubiquitin overexpression allowed partial recovery of translation after heat stress. Taken together, we have shown a requirement for sphingoid bases during the recovery from heat shock and suggest that this reflects a direct lipid-dependent signal to the cap-dependent translation initiation apparatus.
authors.affiliation: Department of Biochemistry, Biozentrum of the University of Basel, CH-4056 Basel, Switzerland.
authors.forename: Karsten D
authors.initials: KD
authors.lastname: Meier
authors.forename: Olivier
authors.initials: O
authors.lastname: Deloche
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kajiwara
authors.forename: Kouichi
authors.initials: K
authors.lastname: Funato
authors.forename: Howard
authors.initials: H
authors.lastname: Riezman
mesh_terms: D001692:Biological Transport; D002518:Ceramides / Q000096:biosynthesis; D020717:Eukaryotic Initiation Factor-2B / Q000378:metabolism; D017353:Gene Deletion; D015870:Gene Expression; D006360:Heat-Shock Proteins / Q000235:genetics; D018869:Heat-Shock Response / Q000235:genetics*; D010442:Peptide Chain Initiation, Translational; D010448:Peptide Initiation Factors / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D015398:Signal Transduction; D013107:Sphingolipids / Q000096:biosynthesis / Q000378:metabolism*; D013489:Suppression, Genetic; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D002518:Ceramides; D020717:Eukaryotic Initiation Factor-2B; D006360:Heat-Shock Proteins; D010448:Peptide Initiation Factors; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D013107:Sphingolipids; D025801:Ubiquitin; C410795:eIF4E-associated protein Eap1; C070972:HsP104 protein, S cerevisiae; D011494:Protein Kinases