Serine-Dependent Sphingolipid Synthesis Is a Metabolic Liability of Aneuploid Cells

Cell Reports

Volumn 21, Issue 13, 2017, Pages 3807-3818

  Hwang, Sunyoung ^a   Gustafsson, H Tobias ^a   O'Sullivan, Ciara ^a   Bisceglia, Gianna ^a   Huang, Xinhe ^b,e   Klose, Christian ^c,f   Schevchenko, Andrej ^c   Dickson, Robert C ^b   Cavaliere, Paola ^d   Dephoure, Noah ^d   Torres, Eduardo M ^a  

^a UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF KENTUCKY   (United States)

^c MAX PLANCK INSTITUTE OF MOLECULAR CELL BIOLOGY AND GENETICS   (Germany)

^d WEILL CORNELL MEDICAL COLLEGE   (United States)

^e SOUTHWEST JIAOTONG UNIVERSITY   (China)

^f LIPOTYPE GMBH   (Germany)

Author keywords

aneuploidy; ceramide; chromosomes; genomic istability; long chain bases; metabolism; myriocin; serine; sphingolipids; sphingosine

Indexed keywords

CERAMIDE; MEMBRANE PROTEIN; PROTEOME; SERINE; SPHINGOLIPID;

ANEUPLOIDY; ARTICLE; CELL METABOLISM; CELL PROLIFERATION; CELL SURVIVAL; CONTROLLED STUDY; ENERGY YIELD; FUNGAL STRAIN; FUNGUS GROWTH; GENE EXPRESSION; GROWTH RATE; LIPIDOMICS; LIPOGENESIS; MASS SPECTROMETRY; NONHUMAN; PRIORITY JOURNAL; YEAST CELL; BIOSYNTHESIS; GENETIC TRANSCRIPTION; GENETICS; METABOLISM; MITOCHONDRION; SACCHAROMYCES CEREVISIAE; UPREGULATION;

ANEUPLOIDY; CELL PROLIFERATION; CERAMIDES; MEMBRANE PROTEINS; MITOCHONDRIA; SACCHAROMYCES CEREVISIAE; SERINE; SPHINGOLIPIDS; TRANSCRIPTION, GENETIC; UP-REGULATION;

EID: 85039950381     PISSN: None     EISSN: 22111247     Source Type: Journal    
DOI: 10.1016/j.celrep.2017.11.103     Document Type: Article

References (54)

1. Alvarez-Vasquez, F., Sims, K.J., Cowart, L.A., Okamoto, Y., Voit, E.O., Hannun, Y.A., Simulation and validation of modelled sphingolipid metabolism in Saccharomyces cerevisiae. Nature 433 (2005), 425–430.
2. Bashore, C., Dambacher, C.M., Goodall, E.A., Matyskiela, M.E., Lander, G.C., Martin, A., Ubp6 deubiquitinase controls conformational dynamics and substrate degradation of the 26S proteasome. Nat. Struct. Mol. Biol. 22 (2015), 712–719.
3. Beach, R.R., Ricci-Tam, C., Brennan, C.M., Moomau, C.A., Hsu, P.H., Hua, B., Silberman, R.E., Springer, M., Amon, A., Aneuploidy causes non-genetic individuality. Cell 169 (2017), 229–242.e21.
4. Beeler, T.J., Fu, D., Rivera, J., Monaghan, E., Gable, K., Dunn, T.M., SUR1 (CSG1/BCL21), a gene necessary for growth of Saccharomyces cerevisiae in the presence of high Ca2+ concentrations at 37 degrees C, is required for mannosylation of inositolphosphorylceramide. Mol. Gen. Genet. 255 (1997), 570–579.
5. Bielawski, J., Pierce, J.S., Snider, J., Rembiesa, B., Szulc, Z.M., Bielawska, A., Comprehensive quantitative analysis of bioactive sphingolipids by high-performance liquid chromatography-tandem mass spectrometry. Methods Mol. Biol. 579 (2009), 443–467.
6. Brace, J.L., Lester, R.L., Dickson, R.C., Rudin, C.M., SVF1 regulates cell survival by affecting sphingolipid metabolism in Saccharomyces cerevisiae. Genetics 175 (2007), 65–76.
7. Cherry, J.M., Hong, E.L., Amundsen, C., Balakrishnan, R., Binkley, G., Chan, E.T., Christie, K.R., Costanzo, M.C., Dwight, S.S., Engel, S.R., et al. Saccharomyces Genome Database: the genomics resource of budding yeast. Nucleic Acids Res. 40 (2012), D700–D705.
8. Chung, N., Mao, C., Heitman, J., Hannun, Y.A., Obeid, L.M., Phytosphingosine as a specific inhibitor of growth and nutrient import in Saccharomyces cerevisiae. J. Biol. Chem. 276 (2001), 35614–35621.
9. Coant, N., Sakamoto, W., Mao, C., Hannun, Y.A., Ceramidases, roles in sphingolipid metabolism and in health and disease. Adv. Biol. Regul. 63 (2017), 122–131.
10. Cowart, L.A., Hannun, Y.A., Selective substrate supply in the regulation of yeast de novo sphingolipid synthesis. J. Biol. Chem. 282 (2007), 12330–12340.
11. Cowart, L.A., Okamoto, Y., Pinto, F.R., Gandy, J.L., Almeida, J.S., Hannun, Y.A., Roles for sphingolipid biosynthesis in mediation of specific programs of the heat stress response determined through gene expression profiling. J. Biol. Chem. 278 (2003), 30328–30338.
12. Cowart, L.A., Shotwell, M., Worley, M.L., Richards, A.J., Montefusco, D.J., Hannun, Y.A., Lu, X., Revealing a signaling role of phytosphingosine-1-phosphate in yeast. Mol. Syst. Biol., 6, 2010, 349.
13. D'mello, N.P., Childress, A.M., Franklin, D.S., Kale, S.P., Pinswasdi, C., Jazwinski, S.M., Cloning and characterization of LAG1, a longevity-assurance gene in yeast. J. Biol. Chem. 269 (1994), 15451–15459.
14. Davoli, T., Xu, A.W., Mengwasser, K.E., Sack, L.M., Yoon, J.C., Park, P.J., Elledge, S.J., Cumulative haploinsufficiency and triplosensitivity drive aneuploidy patterns and shape the cancer genome. Cell 155 (2013), 948–962.
15. Dephoure, N., Hwang, S., O'Sullivan, C., Dodgson, S.E., Gygi, S.P., Amon, A., Torres, E.M., Quantitative proteomic analysis reveals posttranslational responses to aneuploidy in yeast. eLife, 3, 2014, e03023.
16. Dickson, R.C., Lester, R.L., Sphingolipid functions in Saccharomyces cerevisiae. Biochim. Biophys. Acta 1583 (2002), 13–25.
17. Dickson, R.C., Nagiec, E.E., Skrzypek, M., Tillman, P., Wells, G.B., Lester, R.L., Sphingolipids are potential heat stress signals in Saccharomyces. J. Biol. Chem. 272 (1997), 30196–30200.
18. Ejsing, C.S., Sampaio, J.L., Surendranath, V., Duchoslav, E., Ekroos, K., Klemm, R.W., Simons, K., Shevchenko, A., Global analysis of the yeast lipidome by quantitative shotgun mass spectrometry. Proc. Natl. Acad. Sci. USA 106 (2009), 2136–2141.
19. Erez-Roman, R., Pienik, R., Futerman, A.H., Increased ceramide synthase 2 and 6 mRNA levels in breast cancer tissues and correlation with sphingosine kinase expression. Biochem. Biophys. Res. Commun. 391 (2010), 219–223.
20. Fontana, L., Partridge, L., Longo, V.D., Extending healthy life span–from yeast to humans. Science 328 (2010), 321–326.
21. Funato, K., Lombardi, R., Vallee, B., Riezman, H., Lcb4p is a key regulator of ceramide synthesis from exogenous long chain sphingoid base in Saccharomyces cerevisiae. J. Biol. Chem. 278 (2003), 7325–7334.
22. Gasch, A.P., Spellman, P.T., Kao, C.M., Carmel-Harel, O., Eisen, M.B., Storz, G., Botstein, D., Brown, P.O., Genomic expression programs in the response of yeast cells to environmental changes. Mol. Biol. Cell 11 (2000), 4241–4257.
23. Guillermet-Guibert, J., Davenne, L., Pchejetski, D., Saint-Laurent, N., Brizuela, L., Guilbeau-Frugier, C., Delisle, M.B., Cuvillier, O., Susini, C., Bousquet, C., Targeting the sphingolipid metabolism to defeat pancreatic cancer cell resistance to the chemotherapeutic gemcitabine drug. Mol. Cancer Ther. 8 (2009), 809–820.
24. Hanna, J., Hathaway, N.A., Tone, Y., Crosas, B., Elsasser, S., Kirkpatrick, D.S., Leggett, D.S., Gygi, S.P., King, R.W., Finley, D., Deubiquitinating enzyme Ubp6 functions noncatalytically to delay proteasomal degradation. Cell 127 (2006), 99–111.
25. Herbert, A.P., Riesen, M., Bloxam, L., Kosmidou, E., Wareing, B.M., Johnson, J.R., Phelan, M.M., Pennington, S.R., Lian, L.Y., Morgan, A., NMR structure of Hsp12, a protein induced by and required for dietary restriction-induced lifespan extension in yeast. PLoS ONE, 7, 2012, e41975.
26. Jenkins, G.M., Richards, A., Wahl, T., Mao, C., Obeid, L., Hannun, Y., Involvement of yeast sphingolipids in the heat stress response of Saccharomyces cerevisiae. J. Biol. Chem. 272 (1997), 32566–32572.
27. Klose, C., Surma, M.A., Gerl, M.J., Meyenhofer, F., Shevchenko, A., Simons, K., Flexibility of a eukaryotic lipidome–insights from yeast lipidomics. PLoS One, 7, 2012, e35063.
28. Lester, R.L., Dickson, R.C., High-performance liquid chromatography analysis of molecular species of sphingolipid-related long chain bases and long chain base phosphates in Saccharomyces cerevisiae after derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate. Anal. Biochem. 298 (2001), 283–292.
29. Locasale, J.W., Serine, glycine and one-carbon units: cancer metabolism in full circle. Nat. Rev. Cancer 13 (2013), 572–583.
30. Locasale, J.W., Grassian, A.R., Melman, T., Lyssiotis, C.A., Mattaini, K.R., Bass, A.J., Heffron, G., Metallo, C.M., Muranen, T., Sharfi, H., et al. Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis. Nat. Genet. 43 (2011), 869–874.
31. Mandala, S.M., Thornton, R., Tu, Z., Kurtz, M.B., Nickels, J., Broach, J., Menzeleev, R., Spiegel, S., Sphingoid base 1-phosphate phosphatase: a key regulator of sphingolipid metabolism and stress response. Proc. Natl. Acad. Sci. USA 95 (1998), 150–155.
32. McShane, E., Sin, C., Zauber, H., Wells, J.N., Donnelly, N., Wang, X., Hou, J., Chen, W., Storchova, Z., Marsh, J.A., et al. Kinetic analysis of protein stability reveals age-dependent degradation. Cell 167 (2016), 803–815.e21.
33. Morad, S.A., Cabot, M.C., Ceramide-orchestrated signalling in cancer cells. Nat. Rev. Cancer 13 (2013), 51–65.
34. Nagiec, M.M., Nagiec, E.E., Baltisberger, J.A., Wells, G.B., Lester, R.L., Dickson, R.C., Sphingolipid synthesis as a target for antifungal drugs. Complementation of the inositol phosphorylceramide synthase defect in a mutant strain of Saccharomyces cerevisiae by the AUR1 gene. J. Biol. Chem. 272 (1997), 9809–9817.
35. Nickels, J.T., Broach, J.R., A ceramide-activated protein phosphatase mediates ceramide-induced G1 arrest of Saccharomyces cerevisiae. Genes Dev. 10 (1996), 382–394.
36. Oromendia, A.B., Dodgson, S.E., Amon, A., Aneuploidy causes proteotoxic stress in yeast. Genes Dev. 26 (2012), 2696–2708.
37. Pavelka, N., Rancati, G., Zhu, J., Bradford, W.D., Saraf, A., Florens, L., Sanderson, B.W., Hattem, G.L., Li, R., Aneuploidy confers quantitative proteome changes and phenotypic variation in budding yeast. Nature 468 (2010), 321–325.
38. Possemato, R., Marks, K.M., Shaul, Y.D., Pacold, M.E., Kim, D., Birsoy, K., Sethumadhavan, S., Woo, H.K., Jang, H.G., Jha, A.K., et al. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature 476 (2011), 346–350.
39. Qie, L., Nagiec, M.M., Baltisberger, J.A., Lester, R.L., Dickson, R.C., Identification of a Saccharomyces gene, LCB3, necessary for incorporation of exogenous long chain bases into sphingolipids. J. Biol. Chem. 272 (1997), 16110–16117.
40. Roelants, F.M., Breslow, D.K., Muir, A., Weissman, J.S., Thorner, J., Protein kinase Ypk1 phosphorylates regulatory proteins Orm1 and Orm2 to control sphingolipid homeostasis in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 108 (2011), 19222–19227.
41. Saba, J.D., Nara, F., Bielawska, A., Garrett, S., Hannun, Y.A., The BST1 gene of Saccharomyces cerevisiae is the sphingosine-1-phosphate lyase. J. Biol. Chem. 272 (1997), 26087–26090.
42. Santaguida, S., Amon, A., Short- and long-term effects of chromosome mis-segregation and aneuploidy. Nat. Rev. Mol. Cell Biol. 16 (2015), 473–485.
43. Selmecki, A., Forche, A., Berman, J., Aneuploidy and isochromosome formation in drug-resistant Candida albicans. Science 313 (2006), 367–370.
44. Skrzypek, M.S., Nagiec, M.M., Lester, R.L., Dickson, R.C., Inhibition of amino acid transport by sphingoid long chain bases in Saccharomyces cerevisiae. J. Biol. Chem. 273 (1998), 2829–2834.
45. Skrzypek, M.S., Nagiec, M.M., Lester, R.L., Dickson, R.C., Analysis of phosphorylated sphingolipid long-chain bases reveals potential roles in heat stress and growth control in Saccharomyces. J. Bacteriol. 181 (1999), 1134–1140.
46. Stingele, S., Stoehr, G., Peplowska, K., Cox, J., Mann, M., Storchova, Z., Global analysis of genome, transcriptome and proteome reveals the response to aneuploidy in human cells. Mol. Syst. Biol., 8, 2012, 608.
47. Tang, Y.C., Yuwen, H., Wang, K., Bruno, P.M., Bullock, K., Deik, A., Santaguida, S., Trakala, M., Pfau, S.J., Zhong, N., et al. Aneuploid cell survival relies upon sphingolipid homeostasis. Cancer Res. 77 (2017), 5272–5286.
48. Torres, E., Yeast as models of mitotic fidelity. Recent Results Cancer Res. 200 (2015), 143–164.
49. Torres, E.M., Sokolsky, T., Tucker, C.M., Chan, L.Y., Boselli, M., Dunham, M.J., Amon, A., Effects of aneuploidy on cellular physiology and cell division in haploid yeast. Science 317 (2007), 916–924.
50. Torres, E.M., Williams, B.R., Amon, A., Aneuploidy: cells losing their balance. Genetics 179 (2008), 737–746.
51. Torres, E.M., Dephoure, N., Panneerselvam, A., Tucker, C.M., Whittaker, C.A., Gygi, S.P., Dunham, M.J., Amon, A., Identification of aneuploidy-tolerating mutations. Cell 143 (2010), 71–83.
52. Torres, E.M., Springer, M., Amon, A., No current evidence for widespread dosage compensation in S. cerevisiae. eLife, 5, 2016, e10996.
53. Wegner, M.S., Schiffmann, S., Parnham, M.J., Geisslinger, G., Grösch, S., The enigma of ceramide synthase regulation in mammalian cells. Prog. Lipid Res. 63 (2016), 93–119.
54. Yona, A.H., Manor, Y.S., Herbst, R.H., Romano, G.H., Mitchell, A., Kupiec, M., Pilpel, Y., Dahan, O., Chromosomal duplication is a transient evolutionary solution to stress. Proc. Natl. Acad. Sci. USA 109 (2012), 21010–21015.