J Biol Chem, Vol. 273, Issue 37, 23704-23708, September 11, 1998

Bcl-xS and Bad Potentiate the Death Suppressing Activities of Bcl-xL, Bcl-2, and A1 in Yeast

From the Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105

Members of the Bcl-2 family can be grouped into three classes based upon their effects on cell death. The first class suppresses death and includes Bcl-2. A second group, which includes Bax, is lethal, whereas a third class, including Bcl-xS, potentiates killing, although the members are not lethal by themselves. The proteins in the last class are proposed to exert their activity by binding to anti-apoptotic family members, thereby making the cell more susceptible to killing by another agent. To test this hypothesis, an inducible yeast expression system is reported that permits the functional analysis of three Bcl-2 family members. In yeast, Bax is lethal, and this activity is suppressed by Bcl-xL, Bcl-2, and A1. Co-expression of Bcl-xS did not diminish the ability of any of the anti-apoptotic members to antagonize Bax. Rather, co-expression of Bcl-xS potentiated the anti-death activity of all three proteins. This effect was not the result of changes in either the levels or integrity of Bax or anti-apoptotic proteins. Thus, Bcl-xS can bind to anti-apoptotic family members, but this association does not result in loss of biological activity. Therefore, Bcl-xS may act downstream of Bax and in a pathway that is conserved in yeast.