Bcl-2 inhibits a Fas-induced conformational change in the Bax N terminus and Bax mitochondrial translocation

Members of the Bcl-2 family of proteins control the cellular commitment to apoptosis, although their role in Fas-induced apoptosis is ill-defined. In this report we demonstrate that activation of the Fas receptor present on a human breast epithelial cell line resulted in a conformational change in t he N terminus of the pro-apoptotic protein Bar. This conformational change appeared to occur in the cytosol and precede Bar translocation to the mitoc hondria. Overexpression of the anti-apoptotic protein Bcl-2 inhibited both the conformational change of Bar as well as its relocalization to the mitoc hondria. Bcl-2 overexpression did not, however, inhibit Fas-induced cleavag e of both procaspase-8 and the pro-apoptotic protein Bid, indicating that B cl-2 functions downstream of these events. These results suggest that the m echanism by which Bcl-2 inhibits Bar mitochondrial translocation and subseq uent amplification of the apoptotic cascade is not by providing a physical barrier to Bar, but rather by inhibiting an upstream event necessary for Ba r conformational change.