title: Inhibition of IFN-stimulated gene expression and IFN induction of cytolytic resistance to natural killer cell lysis correlate with E1A-p300 binding.
abstract: Treatment of target cells with IFN induces resistance to NK cell lysis. This process is blocked by expression of E1A gene products in adenovirus (Ad)-infected and Ad-transformed cells. We compared the ability of adenovirus serotype 5 (Ad5) E1A exon 1 mutants to inhibit the induction of cytolytic resistance by IFN and block IFN-stimulated gene expression with their capacity to bind the cellular proteins p105 (retinoblastoma gene product), p107, and p300. E1A mutants that did not express conserved region 3 (CR3; residues 138-184) or contained deletions in the nonconserved regions between residues 26-35 or 86-120, bound p105, p107, and p300 and were not impaired in their capacity to block IFN-stimulated gene expression or IFN's induction of cytolytic resistance. E1A mutants with deletions in CR2 (residues 121-138) could not bind p105 or p107, but blocked IFN-stimulated gene expression and IFN's induction of cytolytic resistance. In contrast, mutants in CR1 or the N-terminal nonconserved region (residues 2, 4-25, and 48-60), which define E1A's binding site for p300, were unable to block either IFN-stimulated gene expression or IFN's induction of cytolytic resistance. We conclude that E1A's capacity to block both IFN-stimulated gene expression and IFN's induction of cytolytic resistance appears to be transduced through a pathway that involves E1A-p300 binding. The capacity of E1A to block IFN's induction of cytolytic resistance is probably secondary to E1A's more general ability to inhibit IFN-stimulated gene expression.
authors.affiliation: Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Routes
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: S T
authors.initials: ST
authors.lastname: Bayley
authors.forename: S
authors.initials: S
authors.lastname: Ryan
authors.forename: D J
authors.initials: DJ
authors.lastname: Klemm
mesh_terms: D003602:Cytotoxicity, Immunologic / Q000235:genetics*; D005091:Exons / Q000276:immunology; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007372:Interferons / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology*; D009154:Mutation / Q000276:immunology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D007372:Interferons