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Human, insect and nematode caspases kill Saccharomyces cerevisiae independently of YCA1 and Aif1p

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Abstract

This study characterised the impact of active metazoan apoptotic proteases (caspases) on Saccharomyces cerevisiae viability. Expression of active caspase-3 or caspase-8 in yeast ruptured plasma and nuclear membranes and dramatically impaired clonogenic survival, but did not damage DNA. Deletion of the proposed yeast apoptosis regulators YCA1 or Aif1p did not affect the ability of human, insect or nematode caspases to kill yeast. These data indicate that expression of active metazoan caspases causes irreversible damage to yeast membranes and organelles, in a manner independent of YCA1 and Aif1p.

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References

  1. Herker E, Jungwirth H, Lehmann KA, et al. Chronological aging leads to apoptosis in yeast. J Cell Biol 2004; 164: 501–507.

    Article  PubMed  CAS  Google Scholar 

  2. Madeo F, Frohlich E, Frohlich KU. A yeast mutant showing diagnostic markers of early and late apoptosis. J Cell Biol 1997; 139: 729–734.

    Article  PubMed  CAS  Google Scholar 

  3. Yamaki M, Umehara T, Chimura T, Horikoshi M. Cell death with predominant apoptotic features in Saccharomyces cerevisiae mediated by deletion of the histone chaperone ASF1/CIA1. Genes Cells 2001; 6: 1043–1054.

    Article  PubMed  CAS  Google Scholar 

  4. Qi H, Li TK, Kuo D, Nur EKA, Liu LF. Inactivation of Cdc13p triggers MEC1-dependent apoptotic signals in yeast. J Biol Chem 2003; 278: 15136–15141.

    Article  PubMed  CAS  Google Scholar 

  5. Mitsui K, Nakagawa D, Nakamura M, Okamoto T, Tsurugi K. Valproic acid induces apoptosis dependent of Yca1p at concentrations that mildly affect the proliferation of yeast. FEBS Lett 2005; 579: 723–727.

    Article  PubMed  CAS  Google Scholar 

  6. Laun P, Pichova A, Madeo F, et al. Aged mother cells of Saccharomyces cerevisiae show markers of oxidative stress and apoptosis. Mol Microbiol 2001; 39: 1166–1173.

    Article  PubMed  CAS  Google Scholar 

  7. Uren AG, O’Rourke K, Aravind LA, et al. Identification of paracaspases and metacaspases: Two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma. Mol Cell 2000; 6: 961–967.

    PubMed  CAS  Google Scholar 

  8. Madeo F, Herker E, Maldener C, et al. A caspase-related protease regulates apoptosis in yeast. Mol Cell 2002; 9: 911–917.

    Article  PubMed  CAS  Google Scholar 

  9. Wissing S, Ludovico P, Herker E, et al. An AIF orthologue regulates apoptosis in yeast. J Cell Biol 2004; 166: 969–974.

    Article  PubMed  CAS  Google Scholar 

  10. Hardwick JM, Cheng WC. Mitochondrial programmed cell death pathways in yeast. Dev Cell 2004; 7: 630–632.

    Article  PubMed  CAS  Google Scholar 

  11. Wysocki R, Kron SJ. Yeast cell death during DNA damage arrest is independent of caspase or reactive oxygen species. J Cell Biol 2004; 166: 311–316.

    Article  PubMed  CAS  Google Scholar 

  12. Lowary PT, Widom J. Higher-order structure of Saccharomyces cerevisiae chromatin. Proc Natl Acad Sci USA 1989; 86: 8266–8270.

    Article  PubMed  CAS  Google Scholar 

  13. Watanabe N, Lam E. Two Arabidopsis metacaspases AtMCP1b and AtMCP2b are arginine/lysine-specific cysteine proteases and activate apoptosis-like cell death in yeast. J Biol Chem 2005; 280: 14691–14699.

    Article  PubMed  CAS  Google Scholar 

  14. Hanada M, Aimesempe C, Sato T, Reed JC. Structure-function analysis of Bcl-2 protein identification of conserved domains important for homodimerization with Bcl-2 and heterodimerization with Bax. J Biol Chem 1995; 270: 11962–11969.

    Article  PubMed  CAS  Google Scholar 

  15. Priault M, Camougrand N, Kinnally KW, Vallette FM, Manon S. Yeast as a tool to study Bax/mitochondrial interactions in cell death. FEMS Yeast Res 2003; 4: 15–27.

    Article  PubMed  CAS  Google Scholar 

  16. Hawkins CJ, Wang SL, Hay BA. A cloning method to identify caspases and their regulators in yeast: Identification of Drosophila IAP1 as an inhibitor of the Drosophila caspase DCP-1, Proc Natl Acad Sci 1999; 96: 2885–2890.

    Article  PubMed  CAS  Google Scholar 

  17. Wang SL, Hawkins CJ, Yoo SJ, Muller HA, Hay BA. The Drosophila caspase inhibitor DIAP1 is essential for cell survival and is negatively regulated by REAPER, HID and GRIM, which disrupt DIAP1-caspase interactions. Cell 1999; 98: 453–463.

    Article  PubMed  CAS  Google Scholar 

  18. Hawkins CJ, Yoo SJ, Petersen EP, et al. The Drosophila caspase DRONC cleaves following glutamate or aspartate and is regulated by DIAP1, HID, and GRIM. J Biol Chem 2000; 275: 27084–27093.

    PubMed  CAS  Google Scholar 

  19. Hawkins CJ, Wang SL, Hay BA. Monitoring activity of caspases and their regulators in yeast Saccharomyces cerevisiae. Methods Enzymol 2000; 322: 162–174.

    Article  PubMed  CAS  Google Scholar 

  20. Hawkins CJ, Silke J, Verhagen AM, et al. Analysis of candidate antagonists of IAP-mediated caspase inhibition using yeast reconstituted with the mammalian Apaf-1-activated apoptosis mechanism. Apoptosis 2001; 6: 331–338.

    Article  PubMed  CAS  Google Scholar 

  21. Jabbour AM, Ekert PG, Coulson EJ, et al. The p35 relative, p49, inhibits mammalian and Drosophila caspases including DRONC and protects against apoptosis. Cell Death Differ 2002; 9: 1311–1320.

    Article  PubMed  CAS  Google Scholar 

  22. Jabbour AM, Ho P-k, Puryer MA, et al. The Caenorhabditis elegans CED-9 protein does not directly inhibit the caspase CED-3, in vitro nor in yeast. Cell Death Differ 2004; 11: 1309–1316.

    Article  PubMed  CAS  Google Scholar 

  23. Ho PK, Jabbour AM, Ekert PG, Hawkins CJ. Caspase-2 is resistant to inhibition by inhibitor of apoptosis proteins (IAPs) and can activate caspase-7. FEBS J 2005; 272: 1401–1414.

    Article  PubMed  CAS  Google Scholar 

  24. Kang J, Schaber M, Srinivasula S, et al. Cascades of mammalian caspase activation in the yeast Saccharomyces cerevisiae. J Biol Chem 1999; 274: 3189–3198.

    Article  PubMed  CAS  Google Scholar 

  25. Ekert PG, Silke J, Hawkins CJ, Verhagen A, Vaux DL. DIABLO promotes apoptosis by removing MIHA/XIAP from processed Caspase-9. J Cell Biol 2001; 152: 483–490.

    Article  PubMed  CAS  Google Scholar 

  26. Knight MJ, Riffkin CD, Muscat AM, Ashley DM, Hawkins CJ. Analysis of FasL and TRAIL induced apoptosis pathways in glioma cells. Oncogene 2001; 20: 5789–5798.

    Article  PubMed  CAS  Google Scholar 

  27. Norden C, Liakopoulos D, Barral Y. Dissection of septin actin interactions using actin overexpression in Saccharomyces cerevisiae. Mol Microbiol 2004; 53: 469–483.

    Article  PubMed  CAS  Google Scholar 

  28. Thornberry N, Rano T, Peterson E, et al. A combinatorial approach defines specificities of members of the caspase family and granzyme B. Functional relationships established for key mediators of apoptosis. J Biol Chem 1997; 272: 17907–17911.

    Article  PubMed  CAS  Google Scholar 

  29. Fischer U, Janicke RU, Schulze-Osthoff K. Many cuts to ruin: A comprehensive update of caspase substrates. Cell Death Differ 2003; 10: 76–100.

    Article  PubMed  CAS  Google Scholar 

  30. Mashima T, Naito M, Noguchi K, et al. Actin cleavage by CPP32/apopain during the development of apoptosis. Oncogene 1997; 14: 1007–1012.

    Article  PubMed  CAS  Google Scholar 

  31. Scaffidi C, Fulda S, Srinivasan A, et al. Two CD95 (APO-1/Fas) signaling pathways. EMBO J 1998; 17: 1675–1687.

    Article  PubMed  CAS  Google Scholar 

  32. Degterev A, Boyce M, Yuan J. A decade of caspases. Oncogene 2003; 22: 8543–8567.

    Article  PubMed  CAS  Google Scholar 

  33. Wright ME, Han DK, Carter L, et al. Caspase-3 inhibits growth in Saccharomyces cerevisiae without causing cell death. FEBS Lett 1999; 446: 9–14.

    Article  PubMed  CAS  Google Scholar 

  34. Srinivasula S, Ahmad M, MacFarlane M, et al. Generation of constitutively active recombinant caspases-3 and -6 by rearrangement of their subunits. J Biol Chem 1998; 273: 10107–10111.

    Article  PubMed  CAS  Google Scholar 

  35. Guscetti F, Nath N, Denko N. Functional characterization of human proapoptotic molecules in yeast S. cerevisiae. FASEB J 2005; 19: 464–466.

    PubMed  CAS  Google Scholar 

  36. Severin FF, Hyman AA. Pheromone induces programmed cell death in S. cerevisiae. Curr Biol 2002; 12: R233–R235.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Children’s Cancer Centre, Royal Children’s Hospital, Parkville, 3052, Australia

    M. A. Puryer & C. J. Hawkins

  2. Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, 3052, Australia

    M. A. Puryer & C. J. Hawkins

  3. Department of Paediatrics, University of Melbourne, Parkville 3010, Australia

    C. J. Hawkins

Authors
  1. M. A. Puryer
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  2. C. J. Hawkins
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Correspondence to C. J. Hawkins.

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Puryer, M.A., Hawkins, C.J. Human, insect and nematode caspases kill Saccharomyces cerevisiae independently of YCA1 and Aif1p. Apoptosis 11, 509–517 (2006). https://doi.org/10.1007/s10495-006-5114-2

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  • DOI: https://doi.org/10.1007/s10495-006-5114-2

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