BCL-2, BCL-X(L) AND ADENOVIRUS PROTEIN E1B19KD ARE FUNCTIONALLY EQUIVALENT IN THEIR ABILITY TO INHIBIT CELL-DEATH

Apoptosis is the physiological process by which unwanted cells in an o rganism are killed. Bcl-2, a membrane-bound cytoplasmic protein, is an effective inhibitor of apoptotic cell death induced by many cytotoxic agents. Survival-promoting homologues of Bcl-2 include its close rela tive, Bcl-x(L) and the 19 kD protein encoded by the E1B gene of adenov iruses. Whether these proteins are functionally equivalent and whether they can antagonise all or only some pathways to apoptosis is unresol ved. We have carried out a systematic comparison of Bcl-2, Bcl-x(L) an d adenovirus E1B19kD activity, using several cell lines and a range of cytotoxic conditions. High levels of expression of each of these prot eins inhibited apoptosis induced by growth factor deprivation or treat ment with gamma-radiation, glucocorticoid and various cytotoxic drugs. In contrast, none of them could effectively counter apoptosis induced via the TNF receptor or Fas/APO-1 (CD95). Biochemical analysis reveal ed that all three proteins can associate with Bar and Bah, members of the Bcl-2 protein subfamily that can facilitate apoptosis. The results provide evidence that Bcl-2, Bcl-x(L), and adenovirus protein E1B19kD are indistinguishable in their ability to regulate the cell death eff ector machinery.