Effects of adenovirus E1A protein on interferon-signaling.
We have previously shown that adenovirus E1A proteins can block interferon-alpha (IFN-alpha)-signalling. In the current study, we examined if the same is true for IFN-gamma signaling. Cotransfection experiments showed that both 289R and 243R forms of E1A could block the expression of an IFN-gamma-inducible reporter gene. Similarly, in an E1A-expressing HeLa cell line IFN-gamma failed to induce the synthesis of IRF-1 mRNA. This failure was due to a block in activation of the crucial trans-acting factor, GAF, which in turn was due to the lack of IFN-gamma-activated tyrosine phosphorylation of the STAT1 alpha protein in E1A-expressing cells. The above defect could be attributed to a reduced level of STAT1 alpha protein. The level of p48 protein, which is required for IFN-alpha signaling, was also lowered. However, the level of lak-1 protein, one of the tyrosine kinases necessary for both IFN-alpha and IFN-gamma signalling, was comparable in the E1A-expressing and the control cells. These results indicate that the observed inhibition of IFN signalling in E1A-expressing cells is a consequence of a lower abundance of the necessary trnas-acting factors.
Leonard
G T
GT
Department of Molecular Biology, Cleveland Clinic Foundation, Ohio 44195, USA.
Sen
G C
GC
D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics; D015967:Gene Expression Regulation, Viral; D006367:HeLa Cells; D006801:Humans; D050856:Interferon Regulatory Factor-1; D050832:Interferon-Stimulated Gene Factor 3; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics; D010766:Phosphorylation; D012333:RNA, Messenger; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics; D014443:Tyrosine
D017500:Adenovirus E1A Proteins; D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D050832:Interferon-Stimulated Gene Factor 3; D010750:Phosphoproteins; D012333:RNA, Messenger; D014157:Transcription Factors; C079868:gamma interferon activation factor; D014443:Tyrosine; D007371:Interferon-gamma