Training in Support of Research Project Entitled 'Genetic Regulation of the Bcl-2/Bax Cell Death Pathway'

摘要

The functions of Bcl-2 family proteins in determining the life and death of cells are conserved during evolution. In addition to regulating programmed cell death in mammals, Bcl-2 family proteins can also induce or prevent cell death in the unicellular yeast; overexpression of Bax causes lethality in both S. cerevisiae and S. pombe, and co-expression of either Bcl-2 or Bcl-XL can protect yeast against Bax-caused cell death. On the basis of these observations, we have developed a functional screen and have identified two human genes, BI-1 and BI-2, which inhibit Bax-induced cell death in yeast. Over the past year, we further characterized these two genes and found that both BI-1 and BI-2 are also involved in regulating apoptosis in mammalian cells. Our characterization of these two genes are reported here. Furthermore, we also undertook a yeast genetic screen isolating yeast mutants that are resistant to Bax-mediated lethality. This genetic screen and subsequent complementation cloning have led to the identification of FoF1-ATPase as a requirement for Bax to induce cell death in both yeast and mammalian cells.