NR AWRK

AU Bounhar,Y.; Mann,K.K.; Roucou,X.; LeBlanc,A.C.

TI Prion protein prevents Bax-mediated cell death in the absence of other Bcl-2 family members in Saccharomyces cerevisiae

QU FEMS Yeast Research 2006 Dec; 6(8): 1204-12

PT journal article; research support, n.i.h., extramural; research support, non-u.s. gov't

AB 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.

MH Animals; Apoptosis/*physiology; DNA, Complementary; Humans; Mice; Mitochondria; Prions/genetics/*physiology; Proto-Oncogene Proteins c-bcl-2/physiology; Recombinant Fusion Proteins/genetics/physiology; S Phase/physiology; Saccharomyces cerevisiae/genetics/*physiology; bcl-2-Associated X Protein/genetics/*physiology

AD Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.

SP englisch

PO England

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