FUNCTIONAL SUBSTITUTION IDENTIFIES A CELL-SURVIVAL PROMOTING DOMAIN COMMON TO ADENOVIRUS E1B 19 KDA AND BCL-2 PROTEINS

The adenovirus E1B 19 kDa protein provides a cell survival function du ring adenovirus infection and facilitates efficient virus replication by preventing premature cell death. These functions resemble those per formed by the protein coded by the proto-oncogene Bcl-2. The Bcl-2 pro tein, which provides a survival function in cells exposed to a number of cell death-inducing stimuli, can substitute for the 19 kDa protein during adenovirus infection, Although these two survival-promoting pro teins are not overtly related by primary amino acid sequence, they app ear to share short homologous sequences. In order to determine if thes e sequence motifs constitute common functional domains, we carried out domain exchanges between the 19 kDa and Bcl-2 proteins, Our results i ndicate that a seven amino acid region of the Bcl-2 protein (108-YRRDF AE-114) can efficiently substitute for the corresponding 19 kDa domain (47-YKWEFEE-53). Mutagenizing this domain in Bcl-2 abolishes the surv ival promoting activity of Bcl-2, Substitution of the 19 kDa sequences into Bcl-2 restores the survival promoting activity, albeit at reduce d levels, Our results suggest that this domain (designated NH1) may co nstitute a common functional domain for the 19 kDa protein and surviva l promoting members of the Bcl-2 family of proteins.