Bax- and Bak-induced cell death in the fission yeast Schizosaccharomyces pombe.
The effects of the expression of the human Bcl-2 family proteins Bax, Bak, Bcl-2, and Bcl-XL were examined in the fission yeast Schizosaccharomyces pombe and compared with Bax-induced cell death in mammalian cells. Expression of the proapoptotic proteins Bax and Bak conferred a lethal phenotype in this yeast, which was strongly suppressed by coexpression of the anti-apoptotic protein Bcl-XL. Bcl-2 also partially abrogated Bax-mediated cytotoxicity in S. pombe, whereas a mutant of Bcl-2 (Gly145Ala) that fails to heterodimerize with Bax or block apoptosis in mammalian cells was inactive. However, other features distinguished Bax- and Bak-induced death in S. pombe from animal cell apoptosis. Electron microscopic analysis of S. pombe cells dying in response to Bax or Bak expression demonstrated massive cytosolic vacuolization and multifocal nuclear chromatin condensation, thus distinguishing this form of cell death from the classical morphological features of apoptosis seen in animal cells. Unlike Bax-induced apoptosis in 293 cells that led to the induction of interleukin-1 beta-converting enzyme (ICE)/CED-3-like protease activity, Bax- and Bak-induced cell death in S. pombe was accompanied neither by internucleosomal DNA fragmentation nor by activation of proteases with specificities similar to the ICE/CED-3 family. In addition, the baculovirus protease inhibitor p35, which is a potent inhibitor of ICE/CED-3 family proteases and a blocker of apoptosis in animal cells, failed to prevent cell death induction by Bax or Bak in fission yeast, whereas p35 inhibited Bax-induced cell death in mammalian cells. Taken together, these findings suggest that Bcl-2 family proteins may retain an evolutionarily conserved ability to regulate cell survival and death but also indicate differences in the downstream events that are activated by overexpression of Bax or Bak in divergent cell types.
Jürgensmeier
J M
JM
Burnham Institute, Apoptosis Research Program, La Jolla, California 92037, USA.
Krajewski
S
S
Armstrong
R C
RC
Wilson
G M
GM
Oltersdorf
T
T
Fritz
L C
LC
Reed
J C
JC
Ottilie
S
S
D017209:Apoptosis; D029742:Caenorhabditis elegans Proteins; D020169:Caspases; D002461:Cell Line, Transformed; D003546:Cysteine Endopeptidases / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000502:physiology*; D013997:Time Factors; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
C494772:BAK1 protein, human; C494826:BAX protein, human; C494811:BCL2L1 protein, human; D029742:Caenorhabditis elegans Proteins; D051034:Inhibitor of Apoptosis Proteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014764:Viral Proteins; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C086430:inhibitor of apoptosis, Nucleopolyhedrovirus; D020169:Caspases; D003546:Cysteine Endopeptidases; C089223:ced-3 protein, C elegans