Identification of mouse sphingomyelin synthase 1 as a suppressor of Bax-mediated cell death in yeast.
We have identified mouse sphingomyelin synthase 1 as a novel suppressor of the growth inhibitory effect of heterologously expressed Bax. Yeast cells expressing sphingomyelin synthase 1 were also found to show an increased resistance to a variety of cytotoxic stimuli including hydrogen peroxide, osmotic stress and elevated temperature. Sphingomyelin synthase 1 functions by catalyzing the conversion of ceramide and phosphatidylcholine to sphingomyelin and diacylglycerol. Ceramide is an antiproliferative and proapoptotic sphingolipid whose level increases in response to a variety of stresses. Consistent with its biochemical function, yeast cells expressing sphingomyelin synthase 1 have an enhanced ability to grow in media containing the cell-permeable C2-ceramide analog as well as the ceramide precursor phytosphingosine. We also show that overexpression of AUR1, a potential yeast functional homolog of sphingomyelin synthase, also protects cells from osmotic stress. Taken together, these results suggest that sphingomyelin synthase 1 likely prevents cell death by counteracting stress-mediated accumulation of endogenous sphingolipids.
Yang
Zhao
Z
Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.
Khoury
Chamel
C
Jean-Baptiste
Gaël
G
Greenwood
Michael T
MT
D000818:Animals; D017209:Apoptosis; D002518:Ceramides / Q000494:pharmacology; D006602:Hexosyltransferases / Q000502:physiology; D006358:Hot Temperature; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D009994:Osmolar Concentration; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000254:growth & development*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D017855:Transferases (Other Substituted Phosphate Groups) / Q000502:physiology*; D051028:bcl-2-Associated X Protein / Q000037:antagonists & inhibitors*
D002518:Ceramides; D051028:bcl-2-Associated X Protein; D006861:Hydrogen Peroxide; D006602:Hexosyltransferases; C088714:phosphatidylinositol-ceramide phosphoinositol transferase; D017855:Transferases (Other Substituted Phosphate Groups); C070186:phosphatidylcholine-ceramide phosphocholine transferase; C012491:phytosphingosine; D013110:Sphingosine