 Binding sites for several key transcription factors, including nuclear factor (NF)-kB and various interferon regulatory factor (IRF) proteins, are present.

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Presentation transcript:

 Binding sites for several key transcription factors, including nuclear factor (NF)-kB and various interferon regulatory factor (IRF) proteins, are present in the promoters of both the IFN- β gene (IFNB) and the IFN- λ genes.  The IFNB promoter contains several IRF-binding elements (IBEs) that provide binding sites for phosphorylated IRF3 and/or IRF7. Similar binding sites are also present in the promoters of the IFN- λ genes. Therefore, it appears that the same set of transcription factors that regulate IFNB transcription also control expression of the IFN- genes. Furthermore, expression of the type-III IFN genes is inducible by many of the same stimuli that activate expression of the type-I IFN genes.

 Consistent with their antiviral activity, the IFN- λ s are usually co-expressed together with type-I IFNs by virus infected cells.

Biological functions induced by IFN- λ  the IFN- λ proteins bind and signal through a heterodimeric receptor complex composed of the IFN- λ R1 and IL-10R2 chains.  As shown in Figure,IFN- λ binds initially to the IFN- λ R1 chain, and the binary complex formed by the association of IFN- λ with the IFNlR1 chain causes a rapid conformational change that facilitates recruitment of the IL10R2 chain to the complex.

 Once assembly of the ternary complex is complete,the receptor-associated Janus tyrosine kinases, Jak1 andTyk2, mediate trans-phosphorylation of the receptor chains, resulting in the formation of phosphotyrosine containing peptide motifs on the intracellular domain of the IFN- λ R1 chain.  these phosphorylated peptide motifs provide transient docking sites for the latent cytosolic signal transducer and activator of transcription (STAT) proteins, STAT1 and STAT2.

 Signaling through type I (IFN-a/b) or type-III (IFN-l) IFN receptor complexes results in the formation of a transcription factor complex known as IFN-stimulated gene factor 3 (ISGF3).  This complex consists of three proteins: STAT1, STAT2 and IRF-9.  After it is fully assembled, ISGF3 translocates to the nucleus where it binds to IFN stimulated response elements (ISREs) in the promoters of various IFN- stimulated genes (ISGs).