Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The size distribution of radiolabeled mouse C-243 cell poly-A containing RNA, and SV40 DNA was analyzed electrophoretically before and after incubation with high concentrations of electrophoretically pure murine fibroblast interferon. Using this sensitive assay, no evidence for any nuclease activity directly associated with interferon could be found, under a wide variety of incubation conditions.
Mol Biol Rep 1979 Dec 31
PMID:Lack of detectable nuclease activity in highly purified preparations of murine fibroblast interferon. 23 Dec 2

A kinetic analysis of the action of interferon with different preparations in chick embryo fibroblast cell culture gives additional evidence for interaction of interferon with the cell surface, compatible with the idea that interferon is not taken up by the cells. With certain assumptions the binding constant is in the range of 10(13) [l/Mol].
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PMID:Kinetics of interferon action. 72 May 10

T-cell activation results in the production of multiple lymphokines. Efficient lymphokine gene expression appears to require both T-cell antigen receptor (TCR) signal transduction and an uncharacterized second or costimulatory signal. CD28 is a T-cell differentiation antigen that can generate intracellular signals that synergize with those of the TCR to increase T-cell activation and interleukin-2 (IL-2) gene expression. In these studies, we have examined the effect of CD28 signal transduction on granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 3 (IL-3), and gamma interferon (IFN-gamma) promoter activity. Stimulation of CD28 in the presence of TCR-like signals increases the activity of the GM-CSF, IL-3, and IFN-gamma promoters by three- to sixfold. As previously demonstrated for the IL-2 promoter, the IL-3 and GM-CSF promoters contain distinct elements of similar sequence which specifically bind a CD28-induced nuclear complex. Mutation of the CD28 response elements in the IL-3 and GM-CSF promoters abrogates the CD28-induced activity without affecting phorbol ester- and calcium ionophore-induced activity. UV cross-linking indicates that the CD28-induced nuclear complex contains polypeptides of approximately 35, 36, and 44 kDa. These studies indicate that the TCR and CD28-regulated signal transduction pathways coordinately regulate the transcription of several lymphokines and that the influence of CD28 signals on transcription is mediated by a common complex.
Mol Cell Biol 1992 Oct
PMID:Regulation of T-cell lymphokine gene transcription by the accessory molecule CD28. 132 52

Recombinant human gamma-interferon is dimeric in solution at pH 7-4 as revealed by analytical gel-filtration. It was shown by circular dichroism that decreasing pH to 5.0 does not affect the secondary and tertiary structures of gamma-interferon macromolecule. It was established that heat denaturation process of gamma-interferon obeys the two-state transition model and can be described as the first-order reversible reaction. Temperature dependence of the denaturation-renaturation rate constants was shown to be consistent with the Arrhenius law. The equilibrium value of the denaturation temperature was found. Effective enthalpy of denaturation was determined both by thermodynamic and kinetic approaches. The data obtained showed that in the pH range 7-4 the dimeric IFN-gamma structure may be considered as a single cooperative thermodynamic domain. Thus, it may be concluded that gamma-interferon dimerization is necessary for the existence of the corresponding tertiary structure of the macromolecule.
Mol Biol (Mosk)
PMID:[Study of the structural properties of recombinant gamma-interferon by circular dichroism and differential scanning microcalorimetry]. 133 59

The interferon-induced protein kinase DAI, the double-stranded RNA (dsRNA)-activated inhibitor of translation, plays a key role in regulating protein synthesis in higher cells. Once activated, in a process that involves autophosphorylation, it phosphorylates the initiation factor eIF-2, leading to inhibition of polypeptide chain initiation. The activity of DAI is controlled by RNA regulators, including dsRNA activators and highly structured single-stranded RNAs which block activation by dsRNA. To elucidate the mechanism of activation, we studied the interaction of DAI with RNA duplexes of discrete sizes. Molecules shorter than 30 bp fail to bind stably and do not activate the enzyme, but at high concentrations they prevent activation by long dsRNA. Molecules longer than 30 bp bind and activate the enzyme, with an efficiency that increases with increasing chain length, reaching a maximum at about 85 bp. These dsRNAs fail to activate at high concentrations and also prevent activation by long dsRNA. Analysis of complexes between dsRNA and DAI suggests that at maximal packing the enzyme interacts with as little as a single helical turn of dsRNA (11 bp) but under conditions that allow activation the binding site protects about 80 bp of duplex. When the RNA-binding site is fully occupied with an RNA activator, the complex appears to undergo a conformational change.
Mol Cell Biol 1992 Nov
PMID:Interactions between double-stranded RNA regulators and the protein kinase DAI. 135 46

P68 is a protein kinase expressed by eukaryotic cells, which is inducible by alpha interferon, and is believed to be an important factor in the regulation of viral and cellular protein synthesis. We have previously reported on a monoclonal antibody, TJ4C4, which is able to specifically detect p68 in formalin-fixed, paraffin-embedded tissue. Because of its important role in regulating cellular protein synthesis, we hypothesized that p68 expression would vary among lung neoplasms with level of differentiation and degree of biosynthetic activity. A total of 246 untreated primary pulmonary and pleural neoplasms were studied. The frequency and relative intensity of p68 expression was determined by light microscopic evaluation of ABC immunoperoxidase stained specimens. All categories of tumors studied demonstrated a spectrum of p68 expression. Expression of p68 correlated well with degree of differentiation in squamous cell carcinomas (SQCC) and acinar adenocarcinomas (AAC). Papillary adenocarcinoma (PAC) and bronchioalveolar carcinoma (BAC) expressed low levels of p68, despite their well differentiated appearance. Expression of the antigen in large cell carcinoma (LCC) was higher than that seen in either poorly differentiated AAC or SQCC. Neuroendocrine tumors generally showed low levels of p68 expression with the intermediate variant of small cell carcinoma expressing higher levels of p68 than the classic "oat cell" form (SCC). Carcinoid tumors expressed higher levels of p68 than did atypical carcinoid tumors. Mesotheliomas showed weak expression of p68, limited primarily to areas of glandular differentiation in the epithelioid form.(ABSTRACT TRUNCATED AT 250 WORDS)
Virchows Arch B Cell Pathol Incl Mol Pathol 1992
PMID:Expression of the protein kinase p-68 recognized by the monoclonal antibody TJ4C4 in human lung neoplasms. 135 15

1. The effects of retinoic acid, gamma-interferon, cytosine arabinoside, nerve growth factor, tumor necrosis factor, and 12-O-tetradecanoylphorbol 13-acetate on the human neuroblastoma cell line, LAN-5, were studied. Intracellular levels of acetylcholinesterase, neuron-specific enolase, catecholamines and related neurotransmitters, vasointestinal peptide, and substance P were evaluated after induction. 2. Cell morphology was strongly affected by retinoic acid, gamma-interferon, cytosine arabinoside, and 12-O-tetradecanoylphorbol 13-acetate. The main effects of retinoic acid and gamma-interferon were the loosening of cell clusters and the extension of long neurites; cytosine arabinoside induced cell body swelling and marked neuritogenesis. Following 12-O-tetradecanoylphorbol 13-acetate treatment, the cells became small, round, and neuritic. Conversely, modifications induced by nerve growth factor and tumor necrosis factor were mild. Cell proliferation rate was reduced by retinoic acid, gamma-interferon, cytosine arabinoside, and 12-O-tetradecanoylphorbol 13-acetate, while nerve growth factor and tumor necrosis factor were devoid of effects. 3. Acetylcholinesterase activity was significantly stimulated by retinoic acid and by gamma-interferon. Neuron-specific enolase activity was unaffected by all treatments except 12-O-tetradecanoylphorbol 13-acetate, which enhanced it by 1.6-fold. 4. The cellular catecholamine and related metabolite content was lowered by retinoic acid and gamma-interferon, while cytosine arabinoside and, even more, 12-O-tetradecanoylphorbol 13-acetate showed a stimulatory activity on their intracellular accumulation. 5. Finally, the cell-associated vasointestinal peptide level was strikingly increased by gamma-interferon and, to a lesser extent, by retinoic acid, cytosine arabinoside, and 12-O-tetradecanoylphorbol 13-acetate. 6. It is concluded that the most relevant biochemical changes associated with LAN-5 cells differentiation involve the repertoire of neurotransmitters and neuropeptides. These events vary in quality and in quantity, likely due to the pattern complexity of gene expression triggered by each inducer in determining the diversity of neuronal phenotypes.
Cell Mol Neurobiol 1992 Jun
PMID:A combined evaluation of biochemical and morphological changes during human neuroblastoma cell differentiation. 135 48

2-5A Synthetase is one of the most extensively characterized enzymes induced by interferon (IFN) and is the central enzyme in a pathway that may be involved in the control of cellular proliferation. We examined the activity of this enzyme in normal diploid Syrian hamster cells (FC13) and their neoplastically transformed derivatives (BP6T); the former cell strain possesses regulated proliferative control, while the latter cell line has escaped from this control. A significant threefold increase in 2-5A synthetase activity was observed in density-arrested versus proliferating FC13 cells, whereas endogenous enzyme activity was uniformly low in BP6T cultures. The increase in enzyme activity in FC13 cultures was not accompanied by the production of IFN at a detectable level, but was parallelled by an increase in the intracellular level of 2',5'-oligoadenylate. IFN treatment resulted in a differential induction of enzyme activity depending on the proliferative state of FC13 cells. After IFN treatment, BP6T cells and subconfluent FC13 cells responded similarly with a fivefold increase in enzyme activity, whereas confluent FC13 cells displayed only a 1.4-fold increase. 2-5A Synthetase enzyme activity reflected steady-state mRNA levels in BP6T and subconfluent FC13 cells. In contrast, a noncoordinate regulation of 2-5A synthetase mRNA expression and enzyme activity was detected in confluent FC13 cells, suggesting that posttranscriptional mechanisms may be involved. The different patterns of endogenous and IFN-induced 2-5A synthetase enzyme activity in FC13 and BP6T cells found in this comparative study may represent an alteration fundamental to the loss of proliferative control in transformed cells.
Mol Carcinog 1992
PMID:A proliferation-related constraint on endogenous and interferon-induced 2-5A synthetase activity in normal and neoplastic Syrian hamster cells. 137 23

To identify genes induced during macrophage activation, a cDNA library was prepared from cultures of the RAW 264.7 mouse macrophage cell line that had been treated with conditioned medium from mitogen-stimulated spleen cells, and the cDNA library was screened by differential plaque hybridization. Eleven cDNA clones, designated CRG-1 through CRG-11, corresponding to mRNA species inducible in RAW 264.7 cells by the spleen cell conditioned medium, were isolated. Inductions were not blocked by cycloheximide. All of the mRNAs were inducible by gamma interferon, and some were also inducible by alpha and beta interferons, by lipopolysaccharide, by phorbol 12-myristate 13-acetate, and by the calcium ionophore A23187. Sequencing of the cDNAs revealed that CRG-1, CRG-3, and CRG-5 are cDNAs of recently identified transcription factors IRF-1, zif/268, and LRF-1 respectively. As previously reported, CRG-2 and CRG-10 (MIG) encode new members of the platelet factor 4 family of cytokines. CRG-6 corresponds to a new member of a family of interferon-inducible genes clustered on mouse chromosome 1, CRG-9 corresponds to a prostaglandin synthase homolog, CRG-8 corresponds to beta 2-microglobulin, and CRG-4 corresponds to metallothionein II. CRG-11 contains sequences of a truncated L1Md repetitive element as well as nonrepetitive sequences. The nonrepetitive sequence of CRG-11 as well as the sequences of CRG-7 are not closely related to published sequences. The CRG genes and proteins are of interest because of their involvement in macrophage activation, because of their roles as mediators of the effects of gamma interferon and other pleiotropic agents, and because of their usefulness as tools for studying the signal pathways through which gamma interferon and other inducers exert their effects on gene and protein expression.
Mol Cell Biol 1992 Apr
PMID:A collection of mRNA species that are inducible in the RAW 264.7 mouse macrophage cell line by gamma interferon and other agents. 137 86

The analysis of the antigenic structure of human interferon (IFN)-alpha 1 with a panel of monoclonal antibodies revealed four immunodominant regions. Three of them, recognized by 12 of 14 antibodies were mapped into the aminoterminal portion of IFN-alpha 1 around residues 31-38, 43-53 and 63-85. The region 31-85 proved important also for the antiviral and antiproliferative activity of the IFN-alpha 1 molecule. The antibody recognizing the sequence around residues (54)63-67 also inhibited the cellular binding of IFN-alpha 1 to the high-affinity receptors.
Mol Immunol
PMID:Immunodominant structures in the aminoterminal portion of human interferon alpha 1. 137 30


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