Morphogenesis checkpoint kinase Swe1 is the executor of lipolysis-dependent cell-cycle progression.
Proc Natl Acad Sci U S A
; 112(10): E1077-85, 2015 Mar 10.
Article
in En
| MEDLINE
| ID: mdl-25713391
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Saccharomyces cerevisiae
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Protein-Tyrosine Kinases
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Cell Cycle
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Cell Cycle Proteins
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Saccharomyces cerevisiae Proteins
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Lipolysis
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Morphogenesis
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2015
Document type:
Article
Affiliation country: