The yeast model system as a tool towards the understanding of apoptosis regulation by sphingolipids.

It has been established that sphingolipids are engaged in the regulation of apoptosis both as direct executors and as signalling molecules. However, the peculiarities of this class of bioactive lipids, namely the interconnectivity of their metabolic pathways, the specific subcellular localization where they are generated and the transport mechanisms involved, introduce a considerably high level of complexity in deciphering their role in the signalling and regulation of programmed cell death. Although yeast is undeniably a simple model, the conservation of the sphingolipid metabolism and of the core machinery engaged in regulated cell death has already provided valuable clues to the understanding of metabolic pathways involved in distinct cellular processes, including apoptosis. It can be anticipated that studies using this model system will further unravel mechanisms underlying the regulation of apoptosis by sphingolipids and contribute to novel therapeutic strategies against serious human diseases associated with dysfunction of sphingolipid-dependent cell death programmes.

[1]  S. Morad,et al.  Ceramide-orchestrated signalling in cancer cells , 2012, Nature Reviews Cancer.

[2]  K. Kajiwara,et al.  Perturbation of sphingolipid metabolism induces endoplasmic reticulum stress‐mediated mitochondrial apoptosis in budding yeast , 2012, Molecular microbiology.

[3]  Y. Hannun,et al.  Modulation of Mitochondrial Outer Membrane Permeabilization and Apoptosis by Ceramide Metabolism , 2012, PloS one.

[4]  A. Dannenberg,et al.  Sphingolipid signaling in metabolic disorders. , 2012, Cell metabolism.

[5]  M. Côrte-Real,et al.  Activation of the Hog1p kinase in Isc1p-deficient yeast cells is associated with mitochondrial dysfunction, oxidative stress sensitivity and premature aging , 2012, Mechanisms of Ageing and Development.

[6]  T. Kuwana,et al.  Sphingolipid Metabolism Cooperates with BAK and BAX to Promote the Mitochondrial Pathway of Apoptosis , 2012, Cell.

[7]  Y. Hannun,et al.  Ceramide synthases at the centre of sphingolipid metabolism and biology. , 2012, The Biochemical journal.

[8]  G. Kroemer,et al.  Ceramide triggers metacaspase-independent mitochondrial cell death in yeast , 2011, Cell cycle.

[9]  T. Nishizaki,et al.  Sphingosine induces apoptosis in hippocampal neurons and astrocytes by activating caspase‐3/‐9 via a mitochondrial pathway linked to SDK/14‐3‐3 protein/Bax/cytochrome c , 2011, Journal of cellular physiology.

[10]  L. Galluzzi,et al.  A yeast BH3‐only protein mediates the mitochondrial pathway of apoptosis , 2011, The EMBO journal.

[11]  A. Kihara,et al.  Sphingolipid synthesis is involved in autophagy in Saccharomyces cerevisiae. , 2011, Biochemical and biophysical research communications.

[12]  Kellie J. Sims,et al.  Role for Sit4p‐dependent mitochondrial dysfunction in mediating the shortened chronological lifespan and oxidative stress sensitivity of Isc1p‐deficient cells , 2011, Molecular microbiology.

[13]  Y. Hannun,et al.  Many Ceramides* , 2011, The Journal of Biological Chemistry.

[14]  John Calvin Reed,et al.  Mitochondrial Ceramide-Rich Macrodomains Functionalize Bax upon Irradiation , 2011, PloS one.

[15]  Vincent M. Cascio,et al.  Yeast Bax Inhibitor, Bxi1p, Is an ER-Localized Protein That Links the Unfolded Protein Response and Programmed Cell Death in Saccharomyces cerevisiae , 2011, PloS one.

[16]  F. Bornancin Ceramide kinase: the first decade. , 2011, Cellular signalling.

[17]  Y. Hannun,et al.  Novel Pathway of Ceramide Production in Mitochondria , 2011, The Journal of Biological Chemistry.

[18]  Faisal T Thayyullathil,et al.  Protein phosphatase 1‐dependent dephosphorylation of Akt is the prime signaling event in sphingosine‐induced apoptosis in Jurkat cells , 2011, Journal of cellular biochemistry.

[19]  S. Pitson Regulation of sphingosine kinase and sphingolipid signaling. , 2011, Trends in biochemical sciences.

[20]  Zhou Wang,et al.  C6-ceramide synergistically potentiates the anti-tumor effects of histone deacetylase inhibitors via AKT dephosphorylation and α-tubulin hyperacetylation both in vitro and in vivo , 2011, Cell Death and Disease.

[21]  M. Nikolova-Karakashian,et al.  Ceramide in Stress Response , 2010, Advances in experimental medicine and biology.

[22]  L. Obeid,et al.  Sphingosine kinase: Role in regulation of bioactive sphingolipid mediators in inflammation. , 2010, Biochimie.

[23]  Y. Hannun,et al.  Molecular Systems Biology 6; Article number 349; doi:10.1038/msb.2010.3 Citation: Molecular Systems Biology 6:349 , 2022 .

[24]  D. Green,et al.  The BCL-2 family reunion. , 2010, Molecular cell.

[25]  M. Colombini,et al.  Ceramide and activated Bax act synergistically to permeabilize the mitochondrial outer membrane , 2010, Apoptosis.

[26]  Wei Hu,et al.  Alkaline Ceramidase 3 (ACER3) Hydrolyzes Unsaturated Long-chain Ceramides, and Its Down-regulation Inhibits Both Cell Proliferation and Apoptosis* , 2010, The Journal of Biological Chemistry.

[27]  J. Chambard,et al.  ERK and cell death: Mechanisms of ERK‐induced cell death – apoptosis, autophagy and senescence , 2010, The FEBS journal.

[28]  Y. Noda,et al.  Kei1: a novel subunit of inositolphosphorylceramide synthase, essential for its enzyme activity and Golgi localization. , 2009, Molecular biology of the cell.

[29]  C. Zazueta,et al.  Bax distribution into mitochondrial detergent‐resistant microdomains is related to ceramide and cholesterol content in postischemic hearts , 2009, The FEBS journal.

[30]  M. Weller,et al.  Lysosomal ceramide mediates gemcitabine-induced death of glioma cells , 2009, Journal of Molecular Medicine.

[31]  K. Ulgen,et al.  Molecular facets of sphingolipids: Mediators of diseases , 2009, Biotechnology journal.

[32]  Eigen R. Peralta,et al.  Ceramide starves cells to death by downregulating nutrient transporter proteins , 2008, Proceedings of the National Academy of Sciences.

[33]  M. Konopleva,et al.  Ceramide promotes apoptosis in chronic myelogenous leukemia-derived K562 cells by a mechanism involving caspase-8 and JNK , 2008, Cell cycle.

[34]  L. Obeid,et al.  Ceramidases: regulators of cellular responses mediated by ceramide, sphingosine, and sphingosine-1-phosphate. , 2008, Biochimica et biophysica acta.

[35]  J. Winderickx,et al.  Ydc1p ceramidase triggers organelle fragmentation, apoptosis and accelerated ageing in yeast , 2008, Cellular and Molecular Life Sciences.

[36]  E. Sidransky,et al.  Gaucher disease: mutation and polymorphism spectrum in the glucocerebrosidase gene (GBA) , 2008, Human mutation.

[37]  Yee‐Shin Lin,et al.  Ceramide induces p38 MAPK and JNK activation through a mechanism involving a thioredoxin-interacting protein-mediated pathway. , 2008, Blood.

[38]  J. Zuckerman,et al.  Anti-apoptotic Bcl-2 Family Proteins Disassemble Ceramide Channels* , 2008, Journal of Biological Chemistry.

[39]  Y. Chun,et al.  Ceramide induces p38 MAPK-dependent apoptosis and Bax translocation via inhibition of Akt in HL-60 cells. , 2008, Cancer letters.

[40]  Yusuf A. Hannun,et al.  Principles of bioactive lipid signalling: lessons from sphingolipids , 2008, Nature Reviews Molecular Cell Biology.

[41]  Yang Zhang,et al.  Ceramide induces release of mitochondrial proapoptotic proteins in caspase-dependent and -independent manner in HT-29 cells , 2008, Science in China Series C: Life Sciences.

[42]  S. Hohmann,et al.  Isc1p plays a key role in hydrogen peroxide resistance and chronological lifespan through modulation of iron levels and apoptosis. , 2007, Molecular biology of the cell.

[43]  Y. Hannun,et al.  Isc1 regulates sphingolipid metabolism in yeast mitochondria. , 2007, Biochimica et biophysica acta.

[44]  M. Sousa,et al.  ADP/ATP carrier is required for mitochondrial outer membrane permeabilization and cytochrome c release in yeast apoptosis , 2007, Molecular microbiology.

[45]  S. Milstien,et al.  Autocrine and paracrine roles of sphingosine-1-phosphate , 2007, Trends in Endocrinology & Metabolism.

[46]  T. Fox,et al.  Ceramide Recruits and Activates Protein Kinase C ζ (PKCζ) within Structured Membrane Microdomains* , 2007, Journal of Biological Chemistry.

[47]  T. Hornemann,et al.  Cloning and Initial Characterization of a New Subunit for Mammalian Serine-palmitoyltransferase* , 2006, Journal of Biological Chemistry.

[48]  Bostjan Kobe,et al.  Uses for JNK: the Many and Varied Substrates of the c-Jun N-Terminal Kinases , 2006, Microbiology and Molecular Biology Reviews.

[49]  Fengqin Gao,et al.  Protein phosphatase 2A inactivates Bcl2's antiapoptotic function by dephosphorylation and up-regulation of Bcl2-p53 binding. , 2006, Blood.

[50]  Yutong Zhao,et al.  De novo biosynthesis of dihydrosphingosine-1-phosphate by sphingosine kinase 1 in mammalian cells. , 2006, Cellular signalling.

[51]  Wei Hu,et al.  Golgi alkaline ceramidase regulates cell proliferation and survival by controlling levels of sphingosine and S1P , 2006, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[52]  M. Greenwood,et al.  Identification of mouse sphingomyelin synthase 1 as a suppressor of Bax-mediated cell death in yeast. , 2006, FEMS yeast research.

[53]  Xingming Deng,et al.  Protein Phosphatase 2A Enhances the Proapoptotic Function of Bax through Dephosphorylation* , 2006, Journal of Biological Chemistry.

[54]  R. Duan Alkaline sphingomyelinase: an old enzyme with novel implications. , 2006, Biochimica et biophysica acta.

[55]  Brian A. Hemmings,et al.  Protein kinase B/Akt at a glance , 2005, Journal of Cell Science.

[56]  S. Klassen,et al.  Ceramide activates a mitochondrial p38 mitogen-activated protein kinase: A potential mechanism for loss of mitochondrial transmembrane potential and apoptosis , 2005, Molecular and Cellular Biochemistry.

[57]  R. Schneiter,et al.  Synthesis of Sphingolipids with Very Long Chain Fatty Acids but Not Ergosterol Is Required for Routing of Newly Synthesized Plasma Membrane ATPase to the Cell Surface of Yeast* , 2005, Journal of Biological Chemistry.

[58]  Leah J. Siskind Mitochondrial Ceramide and the Induction of Apoptosis , 2005, Journal of bioenergetics and biomembranes.

[59]  S. Korsmeyer,et al.  Oligomeric Bax is a component of the putative cytochrome c release channel MAC, mitochondrial apoptosis-induced channel. , 2005, Molecular biology of the cell.

[60]  P. Cartron,et al.  Distinct Domains Control the Addressing and the Insertion of Bax into Mitochondria* , 2005, Journal of Biological Chemistry.

[61]  Xingming Deng,et al.  Nicotine Inactivation of the Proapoptotic Function of Bax through Phosphorylation* , 2005, Journal of Biological Chemistry.

[62]  Y. Hannun,et al.  A mitochondrial pool of sphingomyelin is involved in TNFalpha-induced Bax translocation to mitochondria. , 2005, The Biochemical journal.

[63]  Y. Hannun,et al.  The Phosphatidylglycerol/Cardiolipin Biosynthetic Pathway Is Required for the Activation of Inositol Phosphosphingolipid Phospholipase C, Isc1p, during Growth of Saccharomyces cerevisiae* , 2005, Journal of Biological Chemistry.

[64]  H. Riezman,et al.  Lip1p: a novel subunit of acyl‐CoA ceramide synthase , 2005, The EMBO journal.

[65]  F. Vallette,et al.  Studies of the Interaction of Substituted Mutants of BAX with Yeast Mitochondria Reveal That the C-terminal Hydrophobic α-Helix Is a Second ART Sequence and Plays a Role in the Interaction with Anti-apoptotic BCL-xL* , 2004, Journal of Biological Chemistry.

[66]  A. Kihara,et al.  FVT-1 Is a Mammalian 3-Ketodihydrosphingosine Reductase with an Active Site That Faces the Cytosolic Side of the Endoplasmic Reticulum Membrane* , 2004, Journal of Biological Chemistry.

[67]  D. Schmitt,et al.  Subcellular compartmentalization of ceramide metabolism: MAM (mitochondria-associated membrane) and/or mitochondria? , 2004, The Biochemical journal.

[68]  A. Merlo,et al.  Stabilization of Mdm2 via Decreased Ubiquitination Is Mediated by Protein Kinase B/Akt-dependent Phosphorylation* , 2004, Journal of Biological Chemistry.

[69]  Y. Hannun,et al.  The complex life of simple sphingolipids , 2004, EMBO reports.

[70]  S. Jazwinski,et al.  Suppressor analysis points to the subtle role of the LAG1 ceramide synthase gene in determining yeast longevity , 2004, Experimental Gerontology.

[71]  Huifang M. Zhang,et al.  Akt Kinase Activation Blocks Apoptosis in Intestinal Epithelial Cells by Inhibiting Caspase-3 after Polyamine Depletion* , 2004, Journal of Biological Chemistry.

[72]  David A Hildeman,et al.  ×Phosphorylation of Bax Ser184 by Akt Regulates Its Activity and Apoptosis in Neutrophils* , 2004, Journal of Biological Chemistry.

[73]  C. Hallas,et al.  Cathepsin D links TNF-induced acid sphingomyelinase to Bid-mediated caspase-9 and -3 activation , 2004, Cell Death and Differentiation.

[74]  A. Suzuki,et al.  DES2 protein is responsible for phytoceramide biosynthesis in the mouse small intestine. , 2004, The Biochemical journal.

[75]  Shohei Yamaoka,et al.  Expression Cloning of a Human cDNA Restoring Sphingomyelin Synthesis and Cell Growth in Sphingomyelin Synthase-defective Lymphoid Cells* , 2004, Journal of Biological Chemistry.

[76]  A. Kihara,et al.  Identification of the human sphingolipid C4‐hydroxylase, hDES2, and its up‐regulation during keratinocyte differentiation , 2004, FEBS letters.

[77]  M. Lorusso,et al.  Ceramide Induces Release of Pro-Apoptotic Proteins from Mitochondria by Either a Ca2+-Dependent or a Ca2+-Independent Mechanism , 2004, Journal of bioenergetics and biomembranes.

[78]  V. Briner,et al.  Differential binding of ceramide to MEKK1 in glomerular endothelial and mesangial cells. , 2004, Biochimica et biophysica acta.

[79]  Y. Hannun,et al.  Activation and Localization of Inositol Phosphosphingolipid Phospholipase C, Isc1p, to the Mitochondria during Growth of Saccharomyces cerevisiae* , 2004, Journal of Biological Chemistry.

[80]  J. Brouwers,et al.  Identification of a family of animal sphingomyelin synthases , 2004, The EMBO journal.

[81]  C. Sugimoto,et al.  PI3K/Akt and apoptosis: size matters , 2003, Oncogene.

[82]  A. Kihara,et al.  Csg1p and Newly Identified Csh1p Function in Mannosylinositol Phosphorylceramide Synthesis by Interacting with Csg2p* , 2003, Journal of Biological Chemistry.

[83]  Sarah Spiegel,et al.  Sphingosine-1-phosphate: an enigmatic signalling lipid , 2003, Nature Reviews Molecular Cell Biology.

[84]  A. Kihara,et al.  Identification and Characterization of a Novel Human Sphingosine-1-phosphate Phosphohydrolase, hSPP2* , 2003, The Journal of Biological Chemistry.

[85]  Y. Hannun,et al.  Ceramide in apoptosis: an overview and current perspectives. , 2002, Biochimica et biophysica acta.

[86]  M. Aigle,et al.  Rvs161p and Sphingolipids Are Required for Actin Repolarization following Salt Stress , 2002, Eukaryotic Cell.

[87]  A. Bergmann,et al.  Activation of the Drosophila MLK by ceramide reveals TNF-alpha and ceramide as agonists of mammalian MLK3. , 2002, Molecular cell.

[88]  G. Woods,et al.  Mitochondrial cytochrome c release precedes transmembrane depolarisation and caspase-3 activation during ceramide-induced apoptosis of Jurkat T cells , 2002, Apoptosis.

[89]  S. Cory,et al.  The Bcl2 family: regulators of the cellular life-or-death switch , 2002, Nature Reviews Cancer.

[90]  Paula Ludovico,et al.  Cytochrome c release and mitochondria involvement in programmed cell death induced by acetic acid in Saccharomyces cerevisiae. , 2002, Molecular biology of the cell.

[91]  D. Zajonc,et al.  ISC1-encoded inositol phosphosphingolipid phospholipase C is involved in Na+/Li+ halotolerance of Saccharomyces cerevisiae. , 2002, European journal of biochemistry.

[92]  R. Kolesnick,et al.  Ceramide Channels Increase the Permeability of the Mitochondrial Outer Membrane to Small Proteins* , 2002, The Journal of Biological Chemistry.

[93]  E. Heinz,et al.  Identification and Characterization of a Sphingolipid Δ4-Desaturase Family* , 2002, The Journal of Biological Chemistry.

[94]  B. Dörken,et al.  Ceramide induces mitochondrial activation and apoptosis via a Bax-dependent pathway in human carcinoma cells , 2002, Oncogene.

[95]  Y. Hannun,et al.  De Novo Ceramide Regulates the Alternative Splicing of Caspase 9 and Bcl-x in A549 Lung Adenocarcinoma Cells , 2002, The Journal of Biological Chemistry.

[96]  L. Sandirasegarane,et al.  Ceramide-induced Inhibition of Akt Is Mediated through Protein Kinase Cζ , 2002, The Journal of Biological Chemistry.

[97]  D. Oesterhelt,et al.  Lag1p and Lac1p are essential for the Acyl-CoA-dependent ceramide synthase reaction in Saccharomyces cerevisae. , 2001, Molecular biology of the cell.

[98]  J. Heitman,et al.  Phytosphingosine as a Specific Inhibitor of Growth and Nutrient Import in Saccharomyces cerevisiae * , 2001, The Journal of Biological Chemistry.

[99]  Y. Chun,et al.  Bax‐dependent apoptosis induced by ceramide in HL‐60 cells , 2001, FEBS letters.

[100]  K. Gould,et al.  Coordination between fission yeast glucan formation and growth requires a sphingolipase activity. , 2001, Genetics.

[101]  L. Tsai,et al.  Role of AKT kinase in sphingosine‐induced apoptosis in human hepatoma cells , 2001, Journal of cellular physiology.

[102]  R. Rousson,et al.  Temporal relationships between ceramide production, caspase activation and mitochondrial dysfunction in cell lines with varying sensitivity to anti-Fas-induced apoptosis. , 2001, The Biochemical journal.

[103]  J. Caboche,et al.  Ceramide‐induced apoptosis in cortical neurons is mediated by an increase in p38 phosphorylation and not by the decrease in ERK phosphorylation , 2001, The European journal of neuroscience.

[104]  S. Jazwinski,et al.  C26‐CoA‐dependent ceramide synthesis of Saccharomyces cerevisiae is operated by Lag1p and Lac1p , 2001, The EMBO journal.

[105]  A. Bielawska,et al.  Identification of ISC1 (YER019w) as Inositol Phosphosphingolipid Phospholipase C inSaccharomyces cerevisiae * , 2000, The Journal of Biological Chemistry.

[106]  M. Colombini,et al.  The Lipids C2- and C16-Ceramide Form Large Stable Channels , 2000, The Journal of Biological Chemistry.

[107]  M. Kester,et al.  Ceramide Directly Activates Protein Kinase C ζ to Regulate a Stress-activated Protein Kinase Signaling Complex* , 2000, The Journal of Biological Chemistry.

[108]  A. Bielawska,et al.  Cloning and Characterization of a Saccharomyces cerevisiae Alkaline Ceramidase with Specificity for Dihydroceramide* , 2000, The Journal of Biological Chemistry.

[109]  J. Shinoda,et al.  Influence of Bax or Bcl-2 overexpression on the ceramide-dependent apoptotic pathway in glioma cells , 2000, Oncogene.

[110]  S. Spiegel,et al.  Molecular cloning and characterization of a lipid phosphohydrolase that degrades sphingosine-1- phosphate and induces cell death. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[111]  H. Riezman,et al.  Sphingoid base synthesis requirement for endocytosis in Saccharomyces cerevisiae , 2000, The EMBO journal.

[112]  Michael J. Parsons,et al.  Protein Kinase B Regulates T Lymphocyte Survival, Nuclear Factor κb Activation, and Bcl-XL Levels in Vivo , 2000, The Journal of experimental medicine.

[113]  M. Scheid,et al.  Ceramide Inhibits Protein Kinase B/Akt by Promoting Dephosphorylation of Serine 473* , 2000, The Journal of Biological Chemistry.

[114]  K. Heidenreich,et al.  Akt/Protein Kinase B Up-regulates Bcl-2 Expression through cAMP-response Element-binding Protein* , 2000, The Journal of Biological Chemistry.

[115]  K. Gable,et al.  Tsc3p Is an 80-Amino Acid Protein Associated with Serine Palmitoyltransferase and Required for Optimal Enzyme Activity* , 2000, The Journal of Biological Chemistry.

[116]  A. Bielawska,et al.  Cloning of an Alkaline Ceramidase from Saccharomyces cerevisiae , 2000, The Journal of Biological Chemistry.

[117]  Y. Hannun,et al.  Ceramide in the eukaryotic stress response. , 2000, Trends in cell biology.

[118]  A. Cuadrado,et al.  Inhibition of PKB/Akt1 by C2-Ceramide Involves Activation of Ceramide-Activated Protein Phosphatase in PC12 Cells , 2000, Molecular and Cellular Neuroscience.

[119]  J. Martinou,et al.  Bax oligomerization is required for channel-forming activity in liposomes and to trigger cytochrome c release from mitochondria. , 2000, The Biochemical journal.

[120]  W. Schneider-Brachert,et al.  Cathepsin D targeted by acid sphingomyelinase‐derived ceramide , 1999, The EMBO journal.

[121]  J. Romashkova,et al.  NF-κB is a target of AKT in anti-apoptotic PDGF signalling , 1999, Nature.

[122]  E. Kandel,et al.  Akt/Protein Kinase B Inhibits Cell Death by Preventing the Release of Cytochrome c from Mitochondria , 1999, Molecular and Cellular Biology.

[123]  T. Ito,et al.  Ceramide Induces Bcl2 Dephosphorylation via a Mechanism Involving Mitochondrial PP2A* , 1999, The Journal of Biological Chemistry.

[124]  A. Bielawska,et al.  Long Chain Ceramides Activate Protein Phosphatase-1 and Protein Phosphatase-2A , 1999, The Journal of Biological Chemistry.

[125]  W. V. van Blitterswijk,et al.  Ordering of ceramide formation, caspase activation, and mitochondrial changes during CD95- and DNA damage-induced apoptosis. , 1999, The Journal of clinical investigation.

[126]  M. Greenberg,et al.  Akt Promotes Cell Survival by Phosphorylating and Inhibiting a Forkhead Transcription Factor , 1999, Cell.

[127]  M. Priault,et al.  Investigation of bax-induced release of cytochrome c from yeast mitochondria permeability of mitochondrial membranes, role of VDAC and ATP requirement. , 1999, European journal of biochemistry.

[128]  S. Rocha,et al.  Ceramide Induces Cytochrome c Release from Isolated Mitochondria , 1999, The Journal of Biological Chemistry.

[129]  Y. Lazebnik,et al.  Identification of an endogenous dominant-negative short isoform of caspase-9 that can regulate apoptosis. , 1999, Cancer research.

[130]  M. Mumby,et al.  Reversible Phosphorylation of Bcl2 following Interleukin 3 or Bryostatin 1 Is Mediated by Direct Interaction with Protein Phosphatase 2A* , 1998, The Journal of Biological Chemistry.

[131]  S. Jazwinski,et al.  Homologs of the yeast longevity gene LAG1 in Caenorhabditis elegans and human. , 1998, Genome research.

[132]  R. Kolesnick,et al.  BAD Enables Ceramide to Signal Apoptosis via Ras and Raf-1* , 1998, The Journal of Biological Chemistry.

[133]  John Calvin Reed,et al.  Regulation of cell death protease caspase-9 by phosphorylation. , 1998, Science.

[134]  K. Gable,et al.  The Saccharomyces cerevisiae TSC10/YBR265w Gene Encoding 3-Ketosphinganine Reductase Is Identified in a Screen for Temperature-sensitive Suppressors of the Ca2+-sensitive csg2Δ Mutant* , 1998, The Journal of Biological Chemistry.

[135]  J. Slot,et al.  UDP-Galactose:Ceramide Galactosyltransferase Is a Class I Integral Membrane Protein of the Endoplasmic Reticulum* , 1998, The Journal of Biological Chemistry.

[136]  M. Skrzypek,et al.  The LCB4 (YOR171c) and LCB5(YLR260w) Genes of Saccharomyces Encode Sphingoid Long Chain Base Kinases* , 1998, The Journal of Biological Chemistry.

[137]  K. Williams,et al.  The Cellular Trafficking and Zinc Dependence of Secretory and Lysosomal Sphingomyelinase, Two Products of the Acid Sphingomyelinase Gene* , 1998, The Journal of Biological Chemistry.

[138]  R. Roth,et al.  Evidence of insulin-stimulated phosphorylation and activation of the mammalian target of rapamycin mediated by a protein kinase B signaling pathway. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[139]  J C Reed,et al.  Bax directly induces release of cytochrome c from isolated mitochondria. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[140]  R. Lester,et al.  Heat-induced Elevation of Ceramide in Saccharomyces cerevisiae via de Novo Synthesis* , 1998, The Journal of Biological Chemistry.

[141]  H. Jacob,et al.  EbEST: an automated tool using expressed sequence tags to delineate gene structure. , 1998, Genome research.

[142]  J. Zhou,et al.  Identification of the first mammalian sphingosine phosphate lyase gene and its functional expression in yeast. , 1998, Biochemical and biophysical research communications.

[143]  J. Broach,et al.  Sphingoid base 1-phosphate phosphatase: a key regulator of sphingolipid metabolism and stress response. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[144]  K. Hanada,et al.  A Mammalian Homolog of the Yeast LCB1 Encodes a Component of Serine Palmitoyltransferase, the Enzyme Catalyzing the First Step in Sphingolipid Synthesis* , 1997, The Journal of Biological Chemistry.

[145]  Y. Hannun,et al.  Involvement of Yeast Sphingolipids in the Heat Stress Response of Saccharomyces cerevisiae * , 1997, The Journal of Biological Chemistry.

[146]  P. Dent,et al.  Coordinate regulation of stress- and mitogen-activated protein kinases in the apoptotic actions of ceramide and sphingosine. , 1997, Molecular pharmacology.

[147]  K. Gable,et al.  Hydroxylation of Saccharomyces cerevisiae Ceramides Requires Sur2p and Scs7p* , 1997, The Journal of Biological Chemistry.

[148]  R. Lester,et al.  Synthesis of Mannose-(inositol-P)2-ceramide, the Major Sphingolipid in Saccharomyces cerevisiae, Requires the IPT1 (YDR072c) Gene* , 1997, The Journal of Biological Chemistry.

[149]  Y. Hannun,et al.  Identification and Characterization of Saccharomyces cerevisiae Dihydrosphingosine-1-phosphate Phosphatase* , 1997, The Journal of Biological Chemistry.

[150]  L. Peso,et al.  Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. , 1997, Science.

[151]  S. R. Datta,et al.  Akt Phosphorylation of BAD Couples Survival Signals to the Cell-Intrinsic Death Machinery , 1997, Cell.

[152]  S. Garrett,et al.  The BST1 Gene of Saccharomyces cerevisiaeIs the Sphingosine-1-phosphate Lyase* , 1997, The Journal of Biological Chemistry.

[153]  Y Agid,et al.  Mitochondrial Free Radical Signal in Ceramide‐Dependent Apoptosis: A Putative Mechanism for Neuronal Death in Parkinson's Disease , 1997, Journal of neurochemistry.

[154]  C. Hoppel,et al.  Direct Inhibition of Mitochondrial Respiratory Chain Complex III by Cell-permeable Ceramide* , 1997, The Journal of Biological Chemistry.

[155]  O. Linderkamp,et al.  Fas- or Ceramide-induced Apoptosis Is Mediated by a Rac1-regulated Activation of Jun N-terminal Kinase/p38 Kinases and GADD153* , 1997, The Journal of Biological Chemistry.

[156]  R. Lester,et al.  Identification of a Saccharomyces Gene,LCB3, Necessary for Incorporation of Exogenous Long Chain Bases into Sphingolipids* , 1997, The Journal of Biological Chemistry.

[157]  A. Colell,et al.  Direct Effect of Ceramide on the Mitochondrial Electron Transport Chain Leads to Generation of Reactive Oxygen Species , 1997, The Journal of Biological Chemistry.

[158]  G. Laurent,et al.  Influence of Bcl-2 overexpression on the ceramide pathway in daunorubicin-induced apoptosis of leukemic cells , 1997, Oncogene.

[159]  R. Lester,et al.  Sphingolipid Synthesis as a Target for Antifungal Drugs , 1997, The Journal of Biological Chemistry.

[160]  A. Gottschalk,et al.  Anti-immunoglobulin-induced Apoptosis in WEHI 231 Cells Involves the Slow Formation of Ceramide from Sphingomyelin and Is Blocked by bcl-xL* , 1997, The Journal of Biological Chemistry.

[161]  R. Kolesnick,et al.  Kinase Suppressor of Ras Is Ceramide-Activated Protein Kinase , 1997, Cell.

[162]  K. Irie,et al.  TAK1 Mediates the Ceramide Signaling to Stress-activated Protein Kinase/c-Jun N-terminal Kinase* , 1997, The Journal of Biological Chemistry.

[163]  D. Green,et al.  The Release of Cytochrome c from Mitochondria: A Primary Site for Bcl-2 Regulation of Apoptosis , 1997, Science.

[164]  G. Evan,et al.  Suppression of c-Myc-induced apoptosis by Ras signalling through PI(3)K and PKB , 1997, Nature.

[165]  John Calvin Reed,et al.  Bax- and Bak-induced cell death in the fission yeast Schizosaccharomyces pombe. , 1997, Molecular biology of the cell.

[166]  David R. Kaplan,et al.  Regulation of Neuronal Survival by the Serine-Threonine Protein Kinase Akt , 1997, Science.

[167]  R. Kofler,et al.  Ceramides induce a form of apoptosis in human acute lymphoblastic leukemia cells that is inhibited by Bcl‐2, but not by CrmA , 1997, FEBS letters.

[168]  D. Zechner,et al.  Tumor necrosis factor alpha-induced apoptosis in cardiac myocytes. Involvement of the sphingolipid signaling cascade in cardiac cell death. , 1996, The Journal of clinical investigation.

[169]  A. Gomez-Muñoz,et al.  Phosphatidate Phosphohydrolase Catalyzes the Hydrolysis of Ceramide 1-Phosphate, Lysophosphatidate, and Sphingosine 1-Phosphate* , 1996, The Journal of Biological Chemistry.

[170]  L. Zon,et al.  Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis , 1996, Nature.

[171]  J. Broach,et al.  A ceramide-activated protein phosphatase mediates ceramide-induced G1 arrest of Saccharomyces cerevisiae. , 1996, Genes & development.

[172]  D. Brenner,et al.  Ceramide Activates the Stress-activated Protein Kinases (*) , 1995, The Journal of Biological Chemistry.

[173]  D. Fabbro,et al.  PKC zeta is a molecular switch in signal transduction of TNF‐alpha, bifunctionally regulated by ceramide and arachidonic acid. , 1995, The EMBO journal.

[174]  D. Wenger,et al.  Structure and organization of the human galactocerebrosidase (GALC) gene. , 1995, Genomics.

[175]  Y. Hannun,et al.  Retinoblastoma gene product as a downstream target for a ceramide-dependent pathway of growth arrest. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[176]  E. Zinser,et al.  Characterization, quantification and subcellular localization of inositol-containing sphingolipids of the yeast, Saccharomyces cerevisiae. , 1994, European journal of biochemistry.

[177]  R. Lester,et al.  The LCB2 gene of Saccharomyces and the related LCB1 gene encode subunits of serine palmitoyltransferase, the initial enzyme in sphingolipid synthesis. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[178]  A. Horváth,et al.  Ceramide synthesis enhances transport of GPI‐anchored proteins to the Golgi apparatus in yeast. , 1994, The EMBO journal.

[179]  L. Sanz,et al.  Protein kinase C zeta isoform is critical for kappa B-dependent promoter activation by sphingomyelinase. , 1994, The Journal of biological chemistry.

[180]  D. Franklin,et al.  Cloning and characterization of LAG1, a longevity-assurance gene in yeast. , 1994, The Journal of biological chemistry.

[181]  C. Thompson,et al.  bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death , 1993, Cell.

[182]  S. Garrett,et al.  Ceramide-mediated growth inhibition and CAPP are conserved in Saccharomyces cerevisiae. , 1993, The Journal of biological chemistry.

[183]  R. Lester,et al.  Cloning and characterization of LCB1, a Saccharomyces gene required for biosynthesis of the long-chain base component of sphingolipids , 1991, Journal of bacteriology.

[184]  A. Bielawska,et al.  Role of ceramide as a lipid mediator of 1 alpha,25-dihydroxyvitamin D3-induced HL-60 cell differentiation. , 1990, The Journal of biological chemistry.

[185]  Y. Hannun,et al.  Sphingomyelin turnover induced by vitamin D3 in HL-60 cells. Role in cell differentiation. , 1989, The Journal of biological chemistry.

[186]  R. Kolesnick Sphingomyelinase action inhibits phorbol ester-induced differentiation of human promyelocytic leukemic (HL-60) cells. , 1989, The Journal of biological chemistry.

[187]  R. Kolesnick,et al.  1,2-Diacylglycerols, but not phorbol esters, activate a potential inhibitory pathway for protein kinase C in GH3 pituitary cells. Evidence for involvement of a sphingomyelinase. , 1988, The Journal of biological chemistry.

[188]  R. Kolesnick 1,2-Diacylglycerols but not phorbol esters stimulate sphingomyelin hydrolysis in GH3 pituitary cells. , 1987, The Journal of biological chemistry.

[189]  E. P. Kennedy,et al.  Cellular and enzymic synthesis of sphingomyelin. , 1982, Biochemistry.

[190]  S. Roseman,et al.  Enzymatic synthesis of ceramide-glucose and ceramide-lactose by glycosyltransferases from embryonic chicken brain. , 1968, The Journal of biological chemistry.

[191]  W. Kuebler,et al.  vanilloid receptor-like protein, VRL-2 Identification and characterization of a novel human , 2015 .

[192]  Y. Hannun,et al.  The neutral sphingomyelinase family: identifying biochemical connections. , 2011, Advances in enzyme regulation.

[193]  A. Gomez-Muñoz,et al.  Ceramide-1-phosphate in cell survival and inflammatory signaling. , 2010, Advances in experimental medicine and biology.

[194]  E. Gulbins,et al.  Ceramide-enriched membrane domains--structure and function. , 2009, Biochimica et biophysica acta.

[195]  A. Kihara,et al.  Identification and Characterization of a Novel Human Sphingosine-1-phosphate Phosphohydrolase , hSPP 2 * , 2002 .

[196]  R. Lester,et al.  Sphingolipid synthesis: identification and characterization of mammalian cDNAs encoding the Lcb2 subunit of serine palmitoyltransferase. , 1996, Gene.