BH3-only proteins Noxa, Bik, Bmf, and Bid activate Bax and Bak indirectly when studied in yeast model.

BH3-only proteins of the Bcl-2 family regulate programmed cell death in mammals through activation of multidomain proapoptotic proteins Bax and Bak in response to various proapoptotic stimuli by mechanism that remains under dispute. Here, we report that the cell death-promoting activity of BH3-only proteins Bik, Bmf, Noxa, and tBid can only be reconstituted in yeast when both multidomain proapoptotic and antiapoptotic Bcl-2 family proteins are present. Inability of these proteins to induce cell death in the absence of antiapoptotic proteins suggests that all tested BH3-only proteins likely activate Bax and Bak indirectly by inhibiting antiapoptotic proteins.

BH3-only protein Bim inhibits activity of antiapoptotic members of Bcl-2 family when expressed in yeast.

Proteins of the Bcl-2 family regulate programmed cell death in mammals by promoting the release of cytochrome c from mitochondria in response to various proapoptotic stimuli. The mechanism by which BH3-only members of the family activate multidomain proapoptotic proteins Bax and Bak to form a pore in mitochondrial membranes remains under dispute. We report that cell death promoting activity of BH3-only protein Bim can be reconstituted in yeast when both Bax and antiapoptotic protein Bcl-X(L) are present, suggesting that Bim likely activates Bax indirectly by inhibiting antiapoptotic proteins.

Reconstitution of interactions of Murine gammaherpesvirus 68 M11 with Bcl-2 family proteins in yeast.

One of the mechanisms of defense against viral infection is induction of apoptosis in infected cells. To escape this line of protection, genomes of many viruses encode for proteins that inhibit apoptosis. Murid herpesvirus 4 gene M11 encodes for homologue of cellular Bcl-2 proteins that inhibits apoptosis and autophagy in infected cell.