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

J Biol Chem. 2000 Feb 4;275(5):3239-46. doi: 10.1074/jbc.275.5.3239.

Abstract

A 193-kDa SV40 large T antigen (T-Ag)-binding protein, designated p193, was identified and cloned. Inspection of the deduced amino acid sequence revealed 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 promoted apoptosis in NIH-3T3 cells. Deletion of the BH3 motif abolished p193 apoptosis activity. p193-induced apoptosis was antagonized by co-expression of Bcl-X(L). Immune cytologic analysis indicated that p193 is localized to the cytoplasm of transfected cells. p193-induced apoptosis was also antagonized by co-expression of T-Ag, which resulted in the cytoplasmic localization of both proteins. The p193 binding site was mapped to an N-terminal region of T-Ag previously implicated in transforming activity. These results suggest that T-Ag possesses an antiapoptosis activity, independent of p53 sequestration, which is actuated by T-Ag/p193 binding in the cytoplasm.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Antigens, Polyomavirus Transforming / metabolism*
  • Apoptosis*
  • Mice
  • Molecular Sequence Data
  • Proto-Oncogene Proteins c-bcl-2 / chemistry
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Sequence Analysis

Substances

  • Antigens, Polyomavirus Transforming
  • Proto-Oncogene Proteins c-bcl-2