Simian virus 40 large T antigen binds a novel Bcl-2 homology domain 3-containing proapoptosis protein in the cytoplasm

A 193-kDa SV40 large T antigen (T-Ag)-binding protein, designated p193, was identified and cloned. Inspection of the deduced amino acid sequence revea led the presence of a short motif similar to the Bcl-2 homology (BH) domain 3, suggesting that p193 may be a member of a family of apoptosis promoting proteins containing only BH3 motifs, In support of this, p193 expression p romoted apoptosis in NIH-3T3 cells. Deletion of the BH3 motif abolished p19 3 apoptosis activity, p193-induced apoptosis was antagonized by co-expressi on of Bcl-X-L. Immune cytologic analysis indicated that p193 is localized t o the cytoplasm of transfected cells. p193-induced apoptosis was also antag onized by co-expression of T-Ag, which resulted in the cytoplasmic localiza tion of both proteins. The p193 binding site was mapped to an N-terminal re gion of T-Ag previously implicated in transforming activity. These results suggest that T-Ag possesses an antiapoptosis activity, independent of p53 s equestration, which is actuated by T-Ag/p193 binding in the cytoplasm.