Adenovirus E1A and E1B-19K proteins protect human hepatoma cells from transforming growth factor beta1-induced apoptosis.
Primary and some transformed hepatocytes undergo apoptosis in response to transforming growth factor beta1 (TGFbeta). We report that infection with species C human adenovirus conferred resistance to TGFbeta-induced apoptosis in human hepatocellular carcinoma cells (Huh-7). Protection against TGFbeta-mediated cell death in adenovirus-infected cells correlated with the maintenance of normal nuclear morphology, lack of pro-caspases 8 and 3 processing, maintenance of the mitochondrial membrane potential, and lack of cellular DNA degradation. The TGFbeta pro-apoptotic signaling pathway was blocked upstream of mitochondria in adenovirus-infected cells. Both the N-terminal sequences of the E1A proteins and the E1B-19K protein were necessary to protect infected cells against TGFbeta-induced apoptosis.
Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO 63104, United States.
Vera L
VL
Tarakanova
William S M
WS
Wold
D017500:Adenovirus E1A Proteins / Q000502:physiology*; D017501:Adenovirus E1B Proteins / Q000502:physiology*; D000260:Adenoviruses, Human / Q000276:immunology* / Q000472:pathogenicity*; D017209:Apoptosis; D002460:Cell Line; D022781:Hepatocytes / Q000821:virology*; D006801:Humans; D053773:Transforming Growth Factor beta1 / Q000276:immunology*
D017500:Adenovirus E1A Proteins; D017501:Adenovirus E1B Proteins; D053773:Transforming Growth Factor beta1