Prion protein prevents Bax-mediated cell death in the absence of other Bcl-2 family members in Saccharomyces cerevisiae.
Although there is no consensus regarding the normal function of the prion protein, increasing evidence points towards a role in cellular protection against cell death. We have previously shown that prion protein is a potent inhibitor of Bax-induced apoptosis in human primary neurons and in the breast carcinoma MCF-7 cells. Here, we used the yeast Saccharomyces cerevisiae to investigate if the neuroprotective function of prion protein requires other members of the Bcl-2 family given that S. cerevisiae lacks Bcl-2 genes but undergoes a mitochondrial-dependent apoptotic cell death upon exogenous expression of Bax protein. We show that Bax induces cell death and growth inhibition in S. cerevisiae. Prion protein prevents Bax-mediated cell death. Prion protein overcomes Bax-mediated growth arrest in S phase but cannot overcome population growth inhibition because the cells then accumulate in G(2)/M phase. We conclude that prion protein does not require other Bcl-2 family proteins to protect against Bax-mediated cell death.
Bounhar
Younes
Y
Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.
Mann
Koren K
KK
Roucou
Xavier
X
LeBlanc
Andréa C
AC
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D018076:DNA, Complementary; D006801:Humans; D051379:Mice; D008928:Mitochondria; D011328:Prions / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000502:physiology; D016196:S Phase / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000502:physiology*
D018076:DNA, Complementary; D011328:Prions; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D051028:bcl-2-Associated X Protein