Defective binding of IRFs to the initiator element of interleukin-1beta-converting enzyme (ICE) promoter in an interferon-resistant Daudi subline.
To investigate mechanisms of interferon (IFN) resistance, we have established an IFN-resistant Daudi subline (Daudi(res)), which is 1 X 10(4) times more resistant to IFN-alpha than parental cells. Among the IFN-inducible genes examined, only ICE mRNA expression was deficient in Daudi(res) cells. We then analyzed the regulatory mechanisms of ICE transcription, and found that IFN-induced activation of the ICE promoter was dependent on the binding of IRFs to its initiator (Inr) element. Inr binding of IRFs was markedly diminished in Daudi(res) cells, and forced expression of IRF-1 was able to activate the ICE promoter to the level of parental cells. These results suggest that IRFs and their target genes, as represented by ICE in this study, are involved in IFN resistance.
Iwase
S
S
Department of Internal Medicine (Aoto), Jikei University School of Medicine, Tokyo, Japan.
Furukawa
Y
Y
Kikuchi
J
J
Saito
S
S
Nakamura
M
M
Nakayama
R
R
Horiguchi-Yamada
J
J
Yamada
H
H
D001665:Binding Sites; D020170:Caspase 1 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D016898:Interferon-alpha / Q000494:pharmacology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; C494229:IRF2 protein, human; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D016898:Interferon-alpha; D010750:Phosphoproteins; D012097:Repressor Proteins; D014157:Transcription Factors; D020170:Caspase 1