Faculty Collaboration Database

Inhibition of IFN-stimulated gene expression and IFN induction of cytolytic resistance to natural killer cell lysis correlate with E1A-p300 binding. J Immunol 1996 Feb 01;156(3):1055-61

Date

02/01/1996

Pubmed ID

8557979

Scopus ID

2-s2.0-0030032903 (requires institutional sign-in at Scopus site)   22 Citations

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.

Author List

Routes JM, Li H, Bayley ST, Ryan S, Klemm DJ

MESH terms used to index this publication - Major topics in bold

Cytotoxicity, Immunologic
Exons
Gene Deletion
Gene Expression Regulation, Neoplastic
Humans
Immunity, Innate
Interferons
Killer Cells, Natural
Mutation
Nuclear Proteins
Protein Binding
Trans-Activators
Transcription Factors
Tumor Cells, Cultured