E1A second exon requirements for induction of target cell susceptibility to lysis by natural killer cells: implications for the mechanism of action.
The E1A oncogene of adenovirus type 5 induces susceptibility of mammalian cells to lysis by natural killer lymphocytes (NK cells). It is unknown whether sensitization to NK killing is mediated directly by targeting effects of interactions between E1A peptides and cell surface MHC molecules or indirectly by an E1A activity that requires structural integrity of the oncoprotein. To discriminate between these hypotheses, rat and hamster cells expressing wild type E1A were contrasted with those expressing truncated products resulting from E1A termination or deletion mutations. Transfected rat cells, expressing truncated proteins from the E1A first exon that encodes MHC-binding peptides, remained resistant to lysis by NK cells, whereas cells expressing full-length E1A protein were highly susceptible to lysis. Studies of infected hamster cells showed that addition of either of two, nonoverlapping, second exon regions reconstituted cytolytic susceptibility induction by E1A. The results do not support the E1A-peptide-MHC hypothesis, since no single E1A peptide coding region was sufficient to convey cytolytic susceptibility to expresser cells. The data indicate that coordinate functions of the E1A first exon and redundant accessory regions in the second exon are required for E1A-induced susceptibility to NK killing.
Krantz
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Robert W. Lisle Research Laboratory in Immunology and Tumor Cell Biology, Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206, USA.
Routes
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Quinlan
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Cook
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JL
D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000260:Adenoviruses, Human / Q000235:genetics / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D006224:Cricetinae; D005091:Exons; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008647:Mesocricetus; D008969:Molecular Sequence Data; D009857:Oncogenes; D011485:Protein Binding; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley
D017500:Adenovirus E1A Proteins; D015395:Histocompatibility Antigens Class I