Two distinct alpha-interferon-dependent signal transduction pathways may contribute to activation of transcription of the guanylate-binding protein gene.

Decker, Thomas; Lew, D J; Darnell, James

doi:10.1128/mcb.11.10.5147

Cited by 129 publications

(104 citation statements)

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“…Genes The 91-kDa protein was immunoprecipitated with the antiserum against the middle portion of the 91-kDa protein from extracts described in the legend to Fig. 4 IFN-a (15,16).…”

Section: Discussionmentioning

confidence: 99%

“…The GBP gene that is transcriptionally responsive (15,16) to IFN-a and IFN-'y contains an ISRE and an overlapping sequence termed GAS that directs the IFN-'y response. Mutations that rendered the ISRE inactive left the GAS functionally intact for IFN-y and surprisingly for IFN-a responses, implying that the GAS element might also direct an IFN-a response (16). The factor that binds to the GAS of the GBP gene has recently been identified and characterized (17).…”

mentioning

confidence: 99%

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Induction of the Ly-6A/E gene by interferon alpha/beta and gamma requires a DNA element to which a tyrosine-phosphorylated 91-kDa protein binds.

Khan

Shuai

Lindwall

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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148

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The murine Ly-6A/E gene is transcriptionaly induced in cells exposed to interferon a/P or y (IFN-a/13 or IFN-y). Analysis of the 5' flanking sequence using reporter plasmids that contain upstream elements of the Ly-6E gene has previously identified an 850-base-pair IFN-responsive region that lacked an IFN-a-stimulated response element (ISRE), the element present and required for an IFN-a response of a number of genes. Analysis by deletion and stable transfection of the IFN-responsive region ofthe Ly-6E promoter has defined an 80-base-pair region containing an IFN-y activation site (GAS) but no ISRE that alows IFN-y and IFN-a inducibility of the Ly-6E gene. As tested by specific antiserum, a 91-kDa protein known to be activated in IFN-a-or IFN-'treated cells binds to-the GAS element from the Ly-6E promoter. The 91-kDa protein exists as an inactive cytoplasmic precursor and depends on tyrosine phosphorylation for its activation. Thus the same 91-kDa protein appears to act in the signal transduction pathways of both types of IFN for the Ly-6-A/E gene.

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“…Genes The 91-kDa protein was immunoprecipitated with the antiserum against the middle portion of the 91-kDa protein from extracts described in the legend to Fig. 4 IFN-a (15,16).…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Induction of the Ly-6A/E gene by interferon alpha/beta and gamma requires a DNA element to which a tyrosine-phosphorylated 91-kDa protein binds.

Khan

Shuai

Lindwall

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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148

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“…Nuclear extract preparation and electrophoretic mobility shift assay EMSA analysis was performed as previously described (Decker et al, 1991). In brief, a double-stranded oligonucleotide corresponding to the GAS element found within the promoter of the guanylate-binding protein (GBP) gene was synthesized and end-labelled using polynucleotide kinase and [γ-32 P]-adenosine 5′-triphosphate (ATP) and incubated with nuclear extracts for 20 min at room temperature.…”

Section: Electrophoretic Mobility Shift Assaymentioning

confidence: 99%

Sodium butyrate enhances STAT 1 expression in PLC/PRF/5 hepatoma cells and augments their responsiveness to interferon-α

Wc¹,

Chuang²

1999

Br J Cancer

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Interferons (IFNs) are cytokines that are involved in the regulation of diverse cellular functions, including modulation of immune responses, inhibition of proliferation, and induction of resistance to viral and bacterial infection (Gutterman, 1994). IFNs employ a unique signalling pathway for rapid induction of gene expression by utilizing two groups of critical elements to transduce the signals from cell surface receptor to nuclear events. The first is the janus family kinases (JAKs), a group of tyrosine kinases containing JAK1, JAK2, JAK3 and TYK2, and the second is STAT (signal transducers and activators of transcription) proteins, a group of latent cytoplasmic transcription factors which are activated by phosphorylation (Darnell, 1997;Pellegrini and Dusanter-Fourt, 1997). Upon IFN stimulation, receptor-associated JAKs are phosphorylated and activated and these kinases, in turn, phosphorylate and activate STAT proteins which then translocate from cytoplasm to nucleus and direct transcriptional activation of various effector genes. The essential role of JAKs and STATs in IFN signalling pathway has been demonstrated by the IFN-resistant phenotypes of cells lacking the JAK or STAT gene products (Muller et al, 1993;Xu et al, 1994).Recent studies have shown that IFNs are the most promising anti-viral agents for the treatment of patients with chronic hepatitis B. These cytokines have been reported to suppress hepatitis B virus (HBV) enhancer activity, reduce virus replication and activate hepatocellular gene expression in cultured liver cells (Tur-Kaspa et al, 1990;Zhang and McLachlan, 1994). Additionally, results from clinical trials also demonstrated that IFNs caused inhibition of HBV replication and reduction of hepatitis B surface antigen (HBsAg) expression (Alexander et al, 1987;Korenman et al, 1991). These studies suggest that IFNs are useful anti-viral drugs for the treatment of patients with viral hepatitis. However, the use of IFNs in the therapy of liver cancer seems discouraging. Although several studies have shown that IFNs exerted growth-inhibitory effects on human hepatoma cells (Lai et al, 1989;Boue et al, 1990), other works showed that patients with advanced hepatocellular carcinoma were resistant to IFNs (Nair et al, 1985;Sachs et al, 1985). However, the molecular basis of this resistance is not clear.Recent studies have indicated that the responses of cells to IFNs could be modulated by regulating the expression or the activity of JAKs and STATs. It has been found that elevated activity of JAKs enhanced the anti-tumour effects of IFNs to lymphoblastoid cells (Lee et al, 1997). Similarly, induction of STATs gene expression by retinoic acids in IFN-unresponsive breast cancer cells and myeloid leukaemia cells permitted growth inhibition by IFNs (Kolla et al, 1996;Weihua et al, 1997). These data suggest that the resistance of cancer cells to IFNs may be due to a relative deficiency of IFN signalling molecules and argue that overexpression of these signalling molecules may restore the responsiveness o...

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“…32 P primer-extension labeled pI␥RE or GAS probes were incubated with 5 g of nuclear extracts from HK that were either untreated (lanes 1 and 13) or IFN␥-treated (lanes 2-12 and 14 -20). Complexes formed with labeled pI␥RE (GRF) are shown in lanes [1][2][3][4][5][6][7][8][9][10][11][12], and complexes formed with labeled GAS (GAF) are shown in lanes [13][14][15][16][17][18][19][20]. Unlabeled competitor DNA was added as follows: irrelevant (lanes 3 and 4), IRF-1 IFNRE (lanes 5-8), GBP⅐GAS (lanes 9, 10, and 18 -20), GBP⅐ISRE (lanes 11, 16, and 17), pI␥RE (lane 12 and 15).…”

Section: Icam-1 Gene Induction By Ifn␥ Via a Distinct Stat Complexmentioning

confidence: 99%

“…When activated by IFN␥, activated Stat1␣ homodimerizes through Src homology domains (10,11) to form ␥-activated factor (GAF). The Stat1␣ homodimers, after translocation to the nucleus, bind to the ␥-activated site (GAS), first identified in the human guanylate-binding protein (GBP) gene, and initiate gene transcription (8,9,12). Stat1␤ (p84) is an alternatively spliced product of the gene for Stat1 and is a truncated protein that lacks 38 amino acids at the carboxyl end of Stat1.…”

mentioning

confidence: 99%

Interferon γ-dependent Induction of Human Intercellular Adhesion Molecule-1 Gene Expression Involves Activation of a Distinct STAT Protein Complex

Naik

Shibagaki²,

Li³

et al. 1997

Journal of Biological Chemistry

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In response to interferon ␥ (IFN␥), intercellular adhesion molecule-1 (ICAM-1) is expressed on human keratinocytes, a cell type that is critically involved in cutaneous inflammation. An ICAM-1 5 regulatory region palindromic response element, pI␥RE, has been shown to confer IFN␥-dependent transcription enhancement. By electrophoretic mobility shift assays (EMSA), pI␥RE forms a distinct complex with proteins from IFN␥-treated human keratinocytes, termed ␥ response factor (GRF). Binding of GRF is tyrosine phosphorylation-dependent, and mutations of pI␥RE that disrupt the palindromic sequence or alter its spatial relationship abrogate GRF binding. Supershift EMSAs using antibodies to characterized STAT proteins suggest that GRF contains a Stat1␣-like protein; however, non-ICAM-1 IFN␥-responsive elements (REs) known to bind Stat1␣ homodimers fail to compete for GRF binding in EMSA, and pI␥RE does not cross-compete with these REs that complex with homodimeric stat1␣. The pI␥RE⅐GRF complex also displays a distinctly different electrophoretic mobility compared to that of IFN␥REs complexed to homodimeric Stat1␣. These findings indicate that a distinct complex containing a Stat1␣-like protein mediates IFN␥-induced ICAM-1 gene transcription and identifies a subset of IFN␥-responsive genes that appear to be regulated by this complex.

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Two distinct alpha-interferon-dependent signal transduction pathways may contribute to activation of transcription of the guanylate-binding protein gene.

Cited by 129 publications

References 32 publications

Induction of the Ly-6A/E gene by interferon alpha/beta and gamma requires a DNA element to which a tyrosine-phosphorylated 91-kDa protein binds.

Induction of the Ly-6A/E gene by interferon alpha/beta and gamma requires a DNA element to which a tyrosine-phosphorylated 91-kDa protein binds.

Sodium butyrate enhances STAT 1 expression in PLC/PRF/5 hepatoma cells and augments their responsiveness to interferon-α

Interferon γ-dependent Induction of Human Intercellular Adhesion Molecule-1 Gene Expression Involves Activation of a Distinct STAT Protein Complex

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