TNF-alpha signals apoptosis through a bid-dependent conformational change in Bax that is inhibited by E1B 19K

Mol Cell. 2000 Jul;6(1):53-63.


The adenovirus E1B 19K gene product is an inhibitor of apoptosis induced by tumor necrosis factor-alpha (TNF-alpha) during viral infection. We report that E1B 19K inhibited neither caspase-8 activation nor caspase-8-dependent Bid cleavage by TNF-alpha. Rather, TNF-alpha induced a tBid-dependent conformational change in Bax that allowed an interaction between E1B 19K and conformationally altered Bax, which caused inhibition of cytochrome c release and caspase-9 activation. E1B 19K expression interrupted caspase-3 processing, permitting cleavage to remove the p12 subunit but not the prodomain consistent with caspase-8 and not caspase-9 enzymatic activity. Thus, E1B 19K blocks TNF-alpha-mediated death signaling by inhibiting a specific form of Bax that interrupts caspase activation downstream of caspase-8 and upstream of caspase-9.

Publication types

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

MeSH terms

  • Adenovirus E1B Proteins / genetics
  • Adenovirus E1B Proteins / metabolism*
  • Apoptosis / physiology*
  • BH3 Interacting Domain Death Agonist Protein
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Caspases / metabolism
  • Cytochrome c Group / metabolism
  • Enzyme Activation
  • Enzyme Precursors / metabolism
  • HeLa Cells
  • Humans
  • Protein Conformation
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-bcl-2*
  • Signal Transduction
  • Transfection
  • Tumor Necrosis Factor-alpha / metabolism*
  • bcl-2-Associated X Protein


  • Adenovirus E1B Proteins
  • BAX protein, human
  • BH3 Interacting Domain Death Agonist Protein
  • BID protein, human
  • Carrier Proteins
  • Cytochrome c Group
  • Enzyme Precursors
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Necrosis Factor-alpha
  • bcl-2-Associated X Protein
  • CASP3 protein, human
  • CASP8 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Caspases