Modulation of cell death in yeast by the bcl-2 family of proteins

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Abstract

Bcl-2 family members are regulators of cell death. The precise biochemical properties of these proteins are unclear although intrafamily protein-protein association is thought to be involved. To elucidate structure-activity relationships among Bcl-2 proteins and identify the pathways in which they act, an inducible death suppressor assay was developed in yeast. Only Bax and Bak killed yeast via a process that did not require interleukin-1β-converting enzyme-like proteases. Bax/Bak lethality was suppressed by coexpression of Bcl-2 family members that are anti-apoptotic in vertebrates, namely Bcl-xL, Bcl-2, Mcl-1, and A1. Furthermore, Bcl-xL and Bcl-2 suppressed Bax toxicity by distinct mechanisms in yeast. Bad, Bcl-xS, and Ced-9 lacked suppressor activity. These inactive proteins bound to anti- apoptotic members of the Bcl-2 family but not to Bax or Bak. In contrast, most Bcl-2 family proteins that attenuated death bound to Bax and Bak. However, two mutants of Bcl-xL suppressed Bax-induced cell death while hawing no Bax binding activity. Therefore, Bcl-xL functions independently of Bax binding, perhaps by interacting with a common target or promoting a pathway that antagonizes Bax. Thus, the pathways downstream of Bax and Bcl-xL may be conserved between vertebrates and yeast. This suppressor assay could be used to isolate components of these pathways.

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CITATION STYLE

APA

Tao, W., Kurschner, C., & Morgan, J. I. (1997). Modulation of cell death in yeast by the bcl-2 family of proteins. Journal of Biological Chemistry, 272(24), 15547–15552. https://doi.org/10.1074/jbc.272.24.15547

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