title: E1B 19K blocks Bax oligomerization and tumor necrosis factor alpha-mediated apoptosis.
abstract: Tumor necrosis factor alpha (TNF-alpha)-mediated death signaling causes the recruitment of monomeric pro- apoptotic Bax into a 500-kDa protein complex. The adenovirus Bcl-2 homologue, E1B 19K, inhibits TNF-alpha-mediated apoptosis, interacts with Bax, and blocked the formation of the 500-kDa Bax complex. TNF-alpha and truncated Bid induced Bax-Bax cross-linking, indicative of oligomerization, and E1B 19K expression during infection inhibited this TNF-alpha-mediated Bax oligomerization. TNF-alpha signaled conformation changes at the Bax amino and carboxy termini. Exposure of the Bax amino terminus facilitates E1B 19K-Bax binding, which prevented exposure of the carboxy-terminal Bax Bcl-2 homology region 2 epitope. Inhibition of Bax oligomerization by E1B 19K is an activity that bears striking similarity to the means by which bacterial immunity proteins block pore formation by bacterial toxins which have structural homology to Bax.
authors.affiliation: Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, New Jersey 08854.
authors.forename: R
authors.initials: R
authors.lastname: Sundararajan
authors.forename: E
authors.initials: E
authors.lastname: White
mesh_terms: D000256:Adenoviridae; D000257:Adenoviridae Infections / Q000235:genetics* / Q000473:pathology / Q000821:virology; D017501:Adenovirus E1B Proteins / Q000235:genetics*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D019281:Dimerization; D015967:Gene Expression Regulation, Viral; D006367:HeLa Cells; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D051028:bcl-2-Associated X Protein
chemical_list: D017501:Adenovirus E1B Proteins; C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein