BAG-1 has been identified as a Bet-a-binding protein that inhibits apo
ptosis, either alone or in co-operation with Bcl-2. Here we show that
BAG-1 inhibits p53-induced apoptosis in the human tumour cell line Sao
s-2. In contrast, BAG-1 was unable to inhibit the p53-independent path
way induced by apoptin, an apoptosis-inducing protein derived from chi
cken anaemia virus. Whereas BAG-1 seemed to co-operate with Bcl-2 to r
epress p53-induced apoptosis, co-expression of these proteins had no i
nhibitory effect on apoptin-induced apoptosis. Moreover, Bcl-2, and to
some extent also BAG-1, paradoxically enhanced the apoptotic activity
of apoptin. These results demonstrate that p53 and apoptin induce apo
ptosis through independent pathways, which are differentially regulate
d by BAG-1 and Bcl-2.