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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A human transient expression assay was used to examine the inducible transcriptional activation of beta interferon (IFN-beta) and IFN-alpha 1 promoters in a homologous cellular environment. Use of 293 cells, an adenovirus DNA-transformed human embryonic kidney cell line, permitted Sendai virus-inducible expression of IFN-beta-CAT hybrid gene. Introduction of the simian virus 40 (SV40) enhancer 5' or 3' to the IFN-CAT gene increased basal (uninduced) levels of chloramphenicol acetyltransferase (CAT) activity; in one construct the SV40 enhancer--IFN-beta regulatory region combination increased the induced CAT activity 50- to 100-fold, suggesting that this may be a generally useful inducible enhancer-promoter combination. No expression from the IFN-alpha-CAT hybrid gene was detected in 293 cells, indicating that human epithelioid cells lack a factor required for expression of the IFN-alpha promoter. However, when the IFN-alpha regulatory region was combined with the SV40 enhancer, a low level of inducible CAT activity was detected in the human transient system.
Mol Cell Biol 1987 Oct
PMID:Transient expression of the beta interferon promoter in human cells. 282 99

A human transient expression system was used to measure the influence of simian virus 40 T antigen and adenovirus E1a proteins on the activation of alpha interferon subtype 1 (IFN-alpha 1) and IFN-beta promoters linked to the reporter chloramphenicol acetyltransferase gene. Large T-antigen production, amplified by expression plasmid replication in transfected 293 cells, was able to trans activate the IFN-beta promoter 5- to 10-fold, increasing both the constitutive and Sendai virus-induced levels of expression. Surprisingly, the previously quiescent transfected IFN-alpha 1 promoter in T-antigen-expressing cells displayed a level of inducibility similar to IFN-beta. The endogenous IFN-alpha 1 gene was also inducible to a limited extent in cells expressing T antigen. A truncated IFN-beta promoter deleted to position -37 relative to the CAP site was neither inducible nor trans activated by T antigen, suggesting that sequences required for efficient induction were also needed for trans activation. Since 293 cells express adenoviral E1a proteins, experiments were also performed in HeLa cells to assess the relative contribution of T antigen and E1a proteins to IFN trans activation. In HeLa cells, T-antigen coexpression increased the constitutive level of IFN-beta and IFN-alpha 1 promoter activity without augmenting relative inducibility. Coexpression of T antigen and E1a proteins did not have a cooperative effect on type 1 IFN expression.
Mol Cell Biol 1988 Aug
PMID:trans activation of type 1 interferon promoters by simian virus 40 T antigen. 285 Apr 92

Mononuclear cells from the peripheral blood of two patients and from the spleen of one patient, all of whom had hairy cell leukemia, were cultured with a recombinant human leukocyte interferon (RD alpha 2-IFN). The IFN was added at concentrations of 10, 100, 1,000, and 10,000 IU/ml, and the cells were cultured for 1, 3, and 7 days. A cytocidal effect of IFN was observed only on cultured cells from the spleen at day 7. Electron-microscopic observations demonstrated that RD alpha 2-IFN induced the formation of tubuloreticular structures (TRSs) and annulate lamellae (ALs) in hairy cells, as well as in co-isolated non-leukemic cells, from all three patients. Ultrastructural examination revealed a close proximity between ALs and TRSs in co-isolated non-leukemic cells. A variability with respect to the induction of TRSs in hairy cells was observed among the three patients. In two of the three patients, the percentage of hairy cells with TRSs increased with the duration of incubation and with the dose of IFN. In the third patient, few hairy cells showed TRSs after 7 days of incubation with IFN. Our findings indicate that leukemic hairy cells may be heterogenous in their response to IFN.
Virchows Arch B Cell Pathol Incl Mol Pathol 1985
PMID:In vitro response of cells from three patients with hairy cell leukemia to a recombinant leukocyte interferon. 286 37

The classical human interferon-alpha (HuIFN-alpha) gene family is estimated to consist of 15 or more nonallelic members which encode proteins sharing greater than 77% amino acid sequence homology. Low-stringency hybridization with a HuIFN-alpha cDNA probe permitted the isolation of two distinct classes of bovine IFN-alpha genes. The first subfamily (class I) is more closely related to the known HuIFN-alpha genes than to the second subfamily (class II) of bovine IFN-alpha genes. Extensive analysis of the human genome has revealed a HuIFN-alpha gene subfamily corresponding to the class II bovine IFN-alpha genes. The class I human and bovine IFN-alpha genes encode mature IFN polypeptides of 165 to 166 amino acids, whereas the class II IFN-alpha genes encode 172 amino acid proteins. Expression in Escherichia coli of members of both gene subfamilies results in polypeptides having potent antiviral activity. In contrast to previous studies which found no evidence of class II IFN-alpha protein or mRNA expression, we demonstrate that the class I and class II IFN-alpha genes are coordinately induced in response to viral infection.
Mol Cell Biol 1985 Apr
PMID:Two distinct families of human and bovine interferon-alpha genes are coordinately expressed and encode functional polypeptides. 298 69

Synthetic oligonucleotides coding for the yeast invertase secretion signal peptide were fused to the gene for the mature form of human interferon (huIFN-alpha 2). Two plasmids (E3 and F2) were constructed. E3 contained the invertase signal codons in a reading frame with the mature huIFN-alpha 2 gene. F2 had a deletion of the codon for alanine at amino acid residue-5 in the invertase signal and an addition of a methionine codon located between the coding sequences for the invertase signal and mature huIFN-alpha 2. Both hybrid genes were located adjacent to the promoter from the 3-phosphoglycerate kinase gene on the multicopy yeast expression plasmid, YEp1PT. Yeast transformants containing these plasmids produced somewhat more IFN than did the same expression plasmid containing the IFN gene with its human secretion signal sequence. HuIFN-alpha 2, purified from the medium of yeast cells containing E3, was found to be processed at the correct site. The huIFN-alpha 2 made by plasmid F2 was found to be completely processed at the junction between the invertase signal (a variant) and the methionine of methionine-huIFN-alpha 2. These results strongly suggested that the invertase signal (or its variant) attached to huIFN was efficiently recognized by the presumed signal recognition particle and was cleaved by the signal peptidase in the yeast cells. These results also suggested that amino acid changes on the right side of the cleavage site did not necessarily prevent cleavage or secretion.
Mol Cell Biol 1986 May
PMID:Saccharomyces cerevisiae secretes and correctly processes human interferon hybrid proteins containing yeast invertase signal peptides. 302 6

The expression of human leucocyte interferon alpha F gene in plasmid pLM-IFN alpha F-273 is controlled by a hybrid tac (trp-lac) promoter. A structural gene for interferon alpha F is a component of the hybrid operon lacZ'-IFN alpha F-TcR, that contains an E. coli trp-operon intercystronic region. Plasmid pLM IFN alpha F-273--directed interferon synthesis allows to obtain about 10(7) IU/l. This plasmid was cloned in broad-host-range vector plasmid pAYC31. The hybrid bi-repliconed plasmid containing interferon gene as well as its single-repliconed deletion derivatives obtained by the in vivo recombination, were introduced into obligate methylotroph Methylobacillus flagellatum KT and Pseudomonas putida PpG6. Methylotrophic strain and Pseudomonas were able to transcribe the interferon gene from E. coli tac promoter, the yield of interferon being 2-4-fold higher as compared with the one in the initial host.
Mol Gen Mikrobiol Virusol 1987 Aug
PMID:[Expression of the human interferon alpha F gene in the obligate methylotroph Methylobacillus flagellatum KT and Pseudomonas putida]. 311 98

A functioning rat thyroid cell line (FRTL5) was used to study interactions of thyrotropin (TSH) and various cytokines on expression of class I and II major histocompatibility complex (MHC) antigens and on growth stimulation. Only gamma-interferon (gamma-IFN) affected MHC antigen expression, i.e., to enhance class I, that was constitutive, and to induce class II. A concomitant, but probably not directly related, effect of gamma-IFN was to diminish growth stimulation, as effected by TSH and other activators of adenylate cyclase and measured by DNA increase and enhanced incorporation of [3H]thymidine into DNA. Stimulation of growth by tetradecanoylphorbol ester was also decreased by gamma-IFN. These effects of gamma-IFN were mimicked to some degree by tumor necrosis factor but there was major synergism between the two cytokines. Enhanced accumulation of cAMP by TSH and other agents was not diminished in these experiments. Flow cytometry analysis showed that inhibition of growth stimulation involved blocking of the passage of cells from the G0/1 phase to the S phase. The data may have relevance to goiter size in autoimmune thyroid disease.
Mol Cell Endocrinol 1988 Aug
PMID:Effects of gamma-interferon and tumor necrosis factor alpha on thyroid cells: induction of class II antigen and inhibition of growth stimulation. 314 28

A 93-kDa tyrosine protein kinase (p93) identified previously as the gene product of the c-fes proto-oncogene, is highly expressed in HL-60 leukemia cells induced to differentiate to the granulocyte or monocyte phenotype. We have now studied the relationship of p93 to the differentiation process by using a dimethyl sulfoxide (DMSO)-resistant subline of HL-60 cells (HL-60/DMSO) or the parental cell line treated with peptide or protein substrates of p93. Treatment of HL-60/DMSO cells with DMSO induced neither differentiation nor the expression of p93; however, cotreatment with IFN-alpha and DMSO resulted in partial differentiation and the concomitant induction of p93 activity. Treatment of wild-type HL-60 cells by the coaddition of the p93 substrates poly(Glu,Tyr)1:1, poly(Glu,Tyr)4:1, poly(Glu,Ala,Tyr)6:3:1, angiotensin II or vasoactive intestinal peptide with DMSO or IFN-tau partially blocked differentiation and concurrently diminished the induction of p93 activity. The inhibitory concentrations of the p93 substrates were related to their Km values. These results indicate that there is an obligatory association between the expression of p93 and granulocyte/monocyte differentiation in this cell line.
Mol Pharmacol 1988 Apr
PMID:Association of p93c-fes tyrosine protein kinase with granulocytic/monocytic differentiation and resistance to differentiating agents in HL-60 leukemia cells. 316 57

When cells are treated with interferon several new proteins are induced. We have isolated by differential screening two cDNA clones corresponding to human genes inducible by IFN-alpha, termed IFI-4 and IFI-54K. The accumulation of the corresponding mRNA was followed as a function of either IFN dose or of time. The IFI-4 and IFI-54K genes, as well as two previously isolated IFN-inducible genes, namely the IFI-56K and low-molecular-weight 2-5A synthetase, were localized on the human chromosomes. Using cloned probes on Southern blots of DNA from a panel of rodent-human somatic cell hybrids, we have assigned the IFI-4 gene to chromosome 1 and the gene coding for the low-molecular-weight 2-5A synthetase to chromosome 12. We also showed that the IFI-54K and IFI-56K genes, unlike most of the IFN-inducible genes, are syntenic. They are both located on chromosome 10. In addition, evidence is given for the presence of a pseudogene homologous to IFI-56K on chromosome 13.
Somat Cell Mol Genet 1988 Sep
PMID:Cloning and chromosomal location of human genes inducible by type I interferon. 317 63

The precise molecular characteristics and the mode of action of the T cell derived lymphokines which augment antibody production in vitro remain uncertain. The use of ill-defined culture supernatants to dissect the cellular interactions in vitro involved in antibody production can lead to ambiguous results as the factors may act either on a contaminating non-B-lymphoid population or directly on the B lymphocyte. We report herein the development of a system for measuring in vitro primary antibody responses by murine spleen cells in which endogenous lymphokine production has been minimized by the in vivo administration of cytotoxic antibodies to deplete T lymphocytes and the addition of the glucocorticosteroid, dexamethasone, throughout the culture period. Using such an assay, a lymphokine activity was detected which was capable of augmenting the plaque forming cell response. This lymphokine was present in culture supernatant derived from the lectin activation of the T cell lymphoma, LBRM-33 and was distinct from other known B cell activators, notably IL-2 and IFN gamma. Biochemical purification of this activity indicated that it might be identical to granulocyte-macrophage colony stimulating factor (GM-CSF). The use of recombinant-derived GM-CSF protein unambiguously showed the role of this lymphokine in antibody production. These experiments demonstrated for the first time, the involvement of a hematopoietic factor in antigen-specific immune responses. Moreover, these results demonstrated an important regulatory circuit in the generation of antibody producing B cells in which GM-CSF, derived from activated T cells, stimulates macrophage function.
J Mol Cell Immunol 1986
PMID:Regulation of antibody production in vitro by granulocyte-macrophage colony stimulating factor. 333 16


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