The E1B 19K protein associates with lamins in vivo and its proper localization is required for inhibition of apoptosis.
Expression of the E1B 19K protein is required to inhibit apoptosis induced by E1A during adenovirus infection and transformation. E1B 19K is homologous to Bcl-2 in function and the two proteins also share limited amino acid sequence homology. Consequently, the E1B 19K and Bcl-2 proteins bind to and inhibit the cellular death-inducing proteins Bax, Bak and Nbk/Bik. Both E1B 19K and Bcl-2 localize to membranes of the nucleus and the endoplasmic reticulum. In addition to membrane association, and unlike Bcl-2, the E1B 19K protein is found associated with intermediate filament proteins in the cytoplasm and the nuclear lamina and copurifies with the lamins both during infection and transformation. While a membrane targeting domain at the C-terminus of Bcl-2 ensures its proper localization, the mechanism by which the E1B 19K protein localizes is unknown. Not surprisingly, lamin A fragments were cloned from a yeast two-hybrid screen for E1B 19K-interacting proteins. The interaction was demonstrated in yeast and mammalian cells in vivo and in vitro and was unique and specific to E1B 19K, with no interaction evident between Bcl-2 and lamin A. Mutants of lamin A/C which localized inappropriately in the cytoplasm or nucleus but retained E1B 19K binding, interfered with the nuclear envelope and cytoplasmic membrane targeting of the E1B 19K protein. Improper localization impaired the ability of the E1B 19K protein to inhibit apoptosis. Thus, proper localization of the E1B 19K protein is required for its function and the interaction of the E1B 19K protein with lamin A/C may represent a means for nuclear envelope localization.
Rao
L
L
Center for Advanced Biotechnology and Medicine, Cancer Institute of New Jersey and Rutgers University, Piscataway 08854, USA.
Modha
D
D
White
E
E
D017501:Adenovirus E1B Proteins / Q000378:metabolism*; D017209:Apoptosis; D002461:Cell Line, Transformed; D034904:Lamin Type A; D034882:Lamins; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism*; D010449:Peptide Mapping; D011485:Protein Binding; D015003:Yeasts
D017501:Adenovirus E1B Proteins; D034904:Lamin Type A; D034882:Lamins; D009687:Nuclear Proteins