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IFN[alpha] can induce the formation of ISGF3 complex which in turn binds the PD1 promoter and increase its transcription in chronically activated T cells [12, 26].
(10) This pathway involves activation of TANK-binding kinase 1 (TBK1) and I[kappa]B kinase [epsilon] (IKK[epsilon]) followed by nuclear translocation of IRF7, a transcription factor acting directly as a transcription factor for type I IFN promoter and indirectly through its induction of type I IFN and the latter's induction of ISGF3. (70,71) Thus, the RIP2-TRAF3-TBK1-IKKe-IRF7 axis plays a key role in the induction of type I IFN responses via NOD1.
The CXCL10 promoter contains functional binding sites for STAT, NF[kappa]B, IRFs, ISGF3, AP1, and C/EBP[beta] .
Darnell Jr., "Cytoplasmic activation of ISGF3, the positive regulator of interferonalpha-stimulated transcription, reconstituted in vitro," Genes & Development, vol.
Types I and III IFNs activate STAT1 and STAT2, form heterodimers which combine with IFN regulatory factor 9 (IRF9), and form IFN-stimulated gene (ISG) factor 3 (ISGF3) complexes [20-22].
STAT1[alpha] and STAT2 form a trimeric complex with IFN regulatory factor 9 (IRF9), known as ISGF3, followed by nuclear translocation and association with promoters of genes specifically activated by the type I IFNs.
This trimeric complex, called IFN-stimulated gene factor 3 (ISGF3), translocates to the nucleus where it binds to the IFN regulated response element (ISRE) to drive IFN-stimulated gene (ISG) expression .
This complex, called interferon-stimulated gene factor 3 (ISGF3), translocates to the nucleus where it binds interferon-stimulated response elements (ISREs) leading to expression of interferon stimulated genes (ISGs) .
Another member, IRF-9, is expressed constitutively in many cell types and unlike the rest of the IRFs, it functions only when it dimerizes with STAT1 and STAT2 to form an active trimeric complex, known as ISGF3. This complex binds to ISRE and activates ISGs [235, 236].
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- ISG15 ubiquitin-like modifier
- ISG15-specific-processing protease
- ISGF-3 gamma
- ISGF3 p48 subunit