The E1B 19K protein is a potent apoptosis inhibitor and the putative adenovirus 
Bcl-2 homolog. To investigate the mechanism of apoptosis regulation, 
19K-interacting cellular proteins were identified using the yeast two-hybrid 
system, and Bax was one of seven 19-K interacting clones. Residues 50-78 of Bax 
containing a conserved region designated Bcl-2 homology region 3 (BH3) were 
sufficient for specific binding to both the E1B 19K and Bcl-2 proteins. The 
Bax-E1B 19K interaction was detectable in vitro and in lysates from mammalian 
cells, and Bax expression antagonized E1B 19K protein function. bax mRNA and 
protein levels were p53-inducible with kinetics identical to that of 
p21/Waf-1/Cip-1, and E1B 19K and Bcl-2 expression did not affect Bax or 
p21/Waf-1/Cip-1 accumulation. In cells where p53 was mutant, Bax expression 
induced apoptosis, suggesting that Bax was sufficient for apoptosis, and acted 
downstream of p53. p53 may simultaneously activate the transcription of genes 
required for both growth arrest (p21/Waf-1/Cip-1) and death (bax), and E1B 19K 
and Bcl-2 may act distally and function through interaction with and antagonism 
of Bax to prevent apoptosis. With the death pathway disabled, induction of 
growth arrest by p53 can then be manifested.