Adenovirus E1B 19-kDa protein (19K) is a member of the Bcl-2 family of 
suppressors of apoptosis. The suppressors function through heterodimerization 
with the death promoters, Bax and related proteins, thus establishing a set 
point within the cell that determines whether or not apoptosis is executed in 
response to a death signal. Sequence similarities between 19K and Bcl-2 are 
largely restricted to short Bcl-2 homology (BH) domains that mediate interaction 
with Bax. The BH1 sequence in 19K is degenerate but nevertheless contains a 
conserved glycine residue found in all family members that when mutated to 
alanine in Bcl-2 results in loss of Bcl-2 function and ability to dimerize with 
Bax (Yin, X.-M., Oltvai, Z. N., and Korsmeyer, S. J. (1994) Nature 369, 
321-323). Here, we show that the analogous mutation in BH1 of 19K also abrogates 
the anti-apoptotic properties of 19K and its ability to interact with Bax, thus 
establishing the critical importance of this residue within BH1 and the likely 
similarity of Bcl-2 and 19K function. In distinct contrast to Bcl-2, however, 
19K interaction was not detected with Bad, a Bcl-2/Bcl-XL dimerizing protein 
that can potentially regulate a Bax middle dotBcl-2/Bcl-XL survival set point 
and reinstate susceptibility to a death signal. Furthermore, the anti-apoptotic 
function of 19K was not overcome by enforced expression of Bad in transfected 
cells. This feature of 19K may provide adenovirus with a selective advantage in 
evading premature induction of apoptosis by the host cell.