title: Morphogenesis checkpoint kinase Swe1 is the executor of lipolysis-dependent cell-cycle progression.
abstract: Cell growth and division requires the precise duplication of cellular DNA content but also of membranes and organelles. Knowledge about the cell-cycle-dependent regulation of membrane and storage lipid homeostasis is only rudimentary. Previous work from our laboratory has shown that the breakdown of triacylglycerols (TGs) is regulated in a cell-cycle-dependent manner, by activation of the Tgl4 lipase by the major cyclin-dependent kinase Cdc28. The lipases Tgl3 and Tgl4 are required for efficient cell-cycle progression during the G1/S (Gap1/replication phase) transition, at the onset of bud formation, and their absence leads to a cell-cycle delay. We now show that defective lipolysis activates the Swe1 morphogenesis checkpoint kinase that halts cell-cycle progression by phosphorylation of Cdc28 at tyrosine residue 19. Saturated long-chain fatty acids and phytosphingosine supplementation rescue the cell-cycle delay in the Tgl3/Tgl4 lipase-deficient strain, suggesting that Swe1 activity responds to imbalanced sphingolipid metabolism, in the absence of TG degradation. We propose a model by which TG-derived sphingolipids are required to activate the protein phosphatase 2A (PP2A(Cdc55)) to attenuate Swe1 phosphorylation and its inhibitory effect on Cdc28 at the G1/S transition of the cell cycle.
authors.affiliation: Institute of Molecular Biosciences, BioTechMed Graz, University of Graz, A8010 Graz, Austria.
authors.forename: Neha
authors.initials: N
authors.lastname: Chauhan
authors.affiliation: Institute of Molecular Biosciences, BioTechMed Graz, University of Graz, A8010 Graz, Austria.
authors.forename: Myriam
authors.initials: M
authors.lastname: Visram
authors.affiliation: Institute of Molecular Biosciences, BioTechMed Graz, University of Graz, A8010 Graz, Austria.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Cristobal-Sarramian
authors.affiliation: Institute of Molecular Biosciences, BioTechMed Graz, University of Graz, A8010 Graz, Austria.
authors.forename: Florian
authors.initials: F
authors.lastname: Sarkleti
authors.affiliation: Institute of Molecular Biosciences, BioTechMed Graz, University of Graz, A8010 Graz, Austria sepp.kohlwein@uni-graz.at.
authors.forename: Sepp D
authors.identifier: http://orcid.org/0000-0002-1030-0598
authors.initials: SD
authors.lastname: Kohlwein
mesh_terms: D001483:Base Sequence; D055162:Biocatalysis; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D017931:DNA Primers; D008049:Lipase / Q000502:physiology; D008066:Lipolysis / Q000502:physiology*; D009024:Morphogenesis; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000166:cytology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; D017931:DNA Primers; D029701:Saccharomyces cerevisiae Proteins; C099685:SWE1 protein, S cerevisiae; D011505:Protein-Tyrosine Kinases; D008049:Lipase; C476342:TGL3 protein, S cerevisiae; C506904:Tgl4 protein, S cerevisiae
keywords: G1/S transition; cyclin-dependent kinase; lipase; sphingolipid; triglyceride