Adenovirus E1B 19 kDa protein protects against cell death induced by v
iral infection and certain external stimuli. The Bcl-2 protein can fun
ctionally substitute for the E1B 19 kDa protein. To identify cellular
targets for the 19 kDa protein, we used the two-hybrid screen in yeast
. We have isolated cDNAs for three different proteins, designated Nip1
, Nip2, and Nip3, that interact with the 19 kDa protein. Mutational an
alysis indicates that these proteins do not associate with 19 kDa muta
nts defective in suppression of cell death, suggesting a correlation b
etween interaction of these proteins and suppression of cell death. Th
ese proteins also associate with discrete sequence motifs in the Bcl-2
protein that are homologous to motifs of the 19 kDa protein. our resu
lts suggest that two diverse proteins, the E1B 19 kDa and the Bcl-2 pr
oteins, promote cell survival through interaction with a common set of
cellular proteins.