PMID: 11790540, 11355893 In turn, virally induced IFN-alpha/beta activates Jak protein tyrosine kinases (Jak1 and Tyk2), leading to formation of both the ISGF3 transcriptional complex and AAF: the former activates several IFN-inducible genes including IRF-7 [39], whereas the latter mediates activation of the IRF-1 gene by its binding to GAS (IFN-gamma-activated site).

PMID: 11790540 IRF-1 in turn induces genes such as that for iNOS.

PMID: 11790540, 9707562, 9566918, 9541017 This phosphorylated IRF-3 then undergoes nuclear translocation, interacts with coactivators CBP and p300, and primarily activates the IFN-beta promoter. PMID: 11790540, 3805784, 6802744 In this context, it is interesting to note that IFN-alpha/beta are also induced by nonviral, pathogen-associated molecules, such as lipopolysaccharide (LPS) and unmethylated DNA.

PMID: 11790540, 9822609, 9877175, 9786932 Subsequently the de novo produced IRF-7 undergoes virus-induced phosphorylation, similar to IRF-3, and activates the IFN-alpha/beta promoters.

PMID: 11790540, 7559546, 9488451 Briefly, viral infections result in phosphorylation of the constitutively expressed IRF-3 at its carboxy-terminal region, converting it to its active form. PMID: 11790540, 3805784, 6802744 In this context, it is interesting to note that IFN-alpha/beta are also induced by nonviral, pathogen-associated molecules, such as lipopolysaccharide (LPS) and unmethylated DNA.

PMID: 11790540, 7559546, 9488451 Briefly, viral infections result in phosphorylation of the constitutively expressed IRF-3 at its carboxy-terminal region, converting it to its active form. PMID: 11790540, 7559546, 9488451 In fact, IRF-3 interacts with the CREB-binding protein (CBP)/p300 coativators, forming a complex, termed double-stranded RNA-activated factor 1 (DRAF1), for some IFN-inducible genes.

PMID: 11790540, 9707562, 9566918, 9541017 This phosphorylated IRF-3 then undergoes nuclear translocation, interacts with coactivators CBP and p300, and primarily activates the IFN-beta promoter.

PMID: 11790540, 9707562, 9566918, 9541017 This phosphorylated IRF-3 then undergoes nuclear translocation, interacts with coactivators CBP and p300, and primarily activates the IFN-beta promoter. PMID: 11790540, 7559546, 9488451 In fact, IRF-3 interacts with the CREB-binding protein (CBP)/p300 coativators, forming a complex, termed double-stranded RNA-activated factor 1 (DRAF1), for some IFN-inducible genes.

PMID: 11790540, 9822609, 9877175, 9786932 Subsequently the de novo produced IRF-7 undergoes virus-induced phosphorylation, similar to IRF-3, and activates the IFN-alpha/beta promoters. PMID: 11790540, 3805784, 6802744 In this context, it is interesting to note that IFN-alpha/beta are also induced by nonviral, pathogen-associated molecules, such as lipopolysaccharide (LPS) and unmethylated DNA.

PMID: 11790540, 9822609, 9877175, 9786932 Subsequently the de novo produced IRF-7 undergoes virus-induced phosphorylation, similar to IRF-3, and activates the IFN-alpha/beta promoters. PMID: 11790540, 11318879 In the absence of the other, IRF-3 acts on the IFN-beta gene, whereas IRF-7 acts on both IFN-alpha and IFN-beta genes by forming homodimers, and both IRF-3 and IRF-7 are required, functioning as a heterodimer, for amplifying the induction of IFN-beta and certain IFN-alpha family genes. PMID: 11790540, 3805784, 6802744 In this context, it is interesting to note that IFN-alpha/beta are also induced by nonviral, pathogen-associated molecules, such as lipopolysaccharide (LPS) and unmethylated DNA.

PMID: 11790540, 9822609, 9877175, 9786932 Subsequently the de novo produced IRF-7 undergoes virus-induced phosphorylation, similar to IRF-3, and activates the IFN-alpha/beta promoters. PMID: 11790540, 11318879 In the absence of the other, IRF-3 acts on the IFN-beta gene, whereas IRF-7 acts on both IFN-alpha and IFN-beta genes by forming homodimers, and both IRF-3 and IRF-7 are required, functioning as a heterodimer, for amplifying the induction of IFN-beta and certain IFN-alpha family genes. PMID: 11790540, 3805784, 6802744 In this context, it is interesting to note that IFN-alpha/beta are also induced by nonviral, pathogen-associated molecules, such as lipopolysaccharide (LPS) and unmethylated DNA.

PMID: 11790540, 11355893 In turn, virally induced IFN-alpha/beta activates Jak protein tyrosine kinases (Jak1 and Tyk2), leading to formation of both the ISGF3 transcriptional complex and AAF: the former activates several IFN-inducible genes including IRF-7 [39], whereas the latter mediates activation of the IRF-1 gene by its binding to GAS (IFN-gamma-activated site).

PMID: 11790540, 11318879 In the absence of the other, IRF-3 acts on the IFN-beta gene, whereas IRF-7 acts on both IFN-alpha and IFN-beta genes by forming homodimers, and both IRF-3 and IRF-7 are required, functioning as a heterodimer, for amplifying the induction of IFN-beta and certain IFN-alpha family genes.

PMID: 11790540, 11318879 In the absence of the other, IRF-3 acts on the IFN-beta gene, whereas IRF-7 acts on both IFN-alpha and IFN-beta genes by forming homodimers, and both IRF-3 and IRF-7 are required, functioning as a heterodimer, for amplifying the induction of IFN-beta and certain IFN-alpha family genes.

PMID: 11790540, 11318879 In the absence of the other, IRF-3 acts on the IFN-beta gene, whereas IRF-7 acts on both IFN-alpha and IFN-beta genes by forming homodimers, and both IRF-3 and IRF-7 are required, functioning as a heterodimer, for amplifying the induction of IFN-beta and certain IFN-alpha family genes.

PMID: 11790540, 3805784, 6802744 In this context, it is interesting to note that IFN-alpha/beta are also induced by nonviral, pathogen-associated molecules, such as lipopolysaccharide (LPS) and unmethylated DNA.

PMID: 11790540, 3805784, 6802744 In this context, it is interesting to note that IFN-alpha/beta are also induced by nonviral, pathogen-associated molecules, such as lipopolysaccharide (LPS) and unmethylated DNA.

PMID: 11790540 More recently, genetic evidence has indicated that some IFN-inducible genes, such as ISG15 and IP-10, are indeed activated in virally infected cells in the absence of ISGF3 by a mechanism dependent on IRF-3 (in the context of the DRAF1 complex) but not on IRF-7.

PMID: 11790540 More recently, genetic evidence has indicated that some IFN-inducible genes, such as ISG15 and IP-10, are indeed activated in virally infected cells in the absence of ISGF3 by a mechanism dependent on IRF-3 (in the context of the DRAF1 complex) but not on IRF-7.

PMID: 11790540 Moreover, these genes are also activated by ISGF3 in the absence of IRF-3.

PMID: 11790540 Moreover, these genes are also activated by ISGF3 in the absence of IRF-3.

PMID: 11790540, 11355893 By contrast, the induction of other genes, such as 2¡ì-5¡ì oligoadenylate synthetase (OAS) and double-stranded-RNA-dependent protein kinase (PKR) is totally dependent on ISGF3, which cannot directly activate the IFN-alpha/beta genes.

PMID: 11790540 The IFN-alpha/beta stimulation of the homologous receptor complex, termed IFNAR, leads to the formation of two transcriptional activator complexes: IFN-alpha-activated factor (AAF), which is a homodimer of signal transducer and activator of transcription (Stat)1; and IFN-stimulated gene factor 3 (ISGF3), which comprises Stat1, Stat2 and a member of the IRF family, IRF-9 (also known as p48).

PMID: 11790540, 11355893 By contrast, the induction of other genes, such as 2¡ì-5¡ì oligoadenylate synthetase (OAS) and double-stranded-RNA-dependent protein kinase (PKR) is totally dependent on ISGF3, which cannot directly activate the IFN-alpha/beta genes.

PMID: 11790540, 10875919, 9501984 In fibroblasts, IFN-alpha/beta expression is observed even after serum starvation, and IFN-alpha expression in these cells is dependent on IFN-beta for an as-yet-unknown reason.

PMID: 11790540 More recently, we found that the IFN-beta gene is induced in bone marrow macrophages upon stimulation by RANK ligand (receptor activator of NF-kappaB ligand) as a negative regulator of osteoclast differentiation, and that this induction is not dependent on IRFs but on RANKL-induced c-Fos, one of the essential transcriptional factors for osteoclast differentiation.

PMID: 11790540 More recently, we found that the IFN-beta gene is induced in bone marrow macrophages upon stimulation by RANK ligand (receptor activator of NF-kappaB ligand) as a negative regulator of osteoclast differentiation, and that this induction is not dependent on IRFs but on RANKL-induced c-Fos, one of the essential transcriptional factors for osteoclast differentiation.

PMID: 11790540 More recently, we found that the IFN-beta gene is induced in bone marrow macrophages upon stimulation by RANK ligand (receptor activator of NF-kappaB ligand) as a negative regulator of osteoclast differentiation, and that this induction is not dependent on IRFs but on RANKL-induced c-Fos, one of the essential transcriptional factors for osteoclast differentiation.

PMID: 11790540 More recently, we found that the IFN-beta gene is induced in bone marrow macrophages upon stimulation by RANK ligand (receptor activator of NF-kappaB ligand) as a negative regulator of osteoclast differentiation, and that this induction is not dependent on IRFs but on RANKL-induced c-Fos, one of the essential transcriptional factors for osteoclast differentiation.

PMID: 11790540, 9541017, 9660935, 9446577 We also speculate that IFN-beta represents the prototype IFN gene, which is subject to induction by a various factors such as IRF-3, c-Fos and NF-kappaB.

PMID: 11790540 More recently, we found that the IFN-beta gene is induced in bone marrow macrophages upon stimulation by RANK ligand (receptor activator of NF-kappaB ligand) as a negative regulator of osteoclast differentiation, and that this induction is not dependent on IRFs but on RANKL-induced c-Fos, one of the essential transcriptional factors for osteoclast differentiation.

PMID: 11790540 The latter mediates activation of the IRF-1 gene by its binding to GAS (IFN-gamma-activated site).

PMID: 11790540, 8197455 ISGF3 binds to cis elements, termed IFN-stimulated response elements (ISREs; consensus sequence A/GNGAAANNGAAACT), which usually reside within the promoter region of IFN-inducible genes [5].

PMID: 11790540 The IFN-alpha/beta stimulation of the homologous receptor complex, termed IFNAR, leads to the formation of two transcriptional activator complexes: IFN-alpha-activated factor (AAF), which is a homodimer of signal transducer and activator of transcription (Stat)1; and IFN-stimulated gene factor 3 (ISGF3), which comprises Stat1, Stat2 and a member of the IRF family, IRF-9 (also known as p48).

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PMID: 11790540 The latter mediates activation of the IRF-1 gene by its binding to GAS (IFN-gamma-activated site).

PMID: 11790540 The latter mediates activation of the IRF-1 gene by its binding to GAS (IFN-gamma-activated site).

PMID: 11790540, 8197455 ISGF3 binds to cis elements, termed IFN-stimulated response elements (ISREs; consensus sequence A/GNGAAANNGAAACT), which usually reside within the promoter region of IFN-inducible genes [5].

PMID: 11790540, 11355893 The former activates several IFN-inducible genes including IRF-7.

PMID: 11790540, 2342456, 7687740 ISREs are also known to bind and be activated by IRF-1.