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)

Regulation of replicative functions in the Epstein-Barr virus (EBV) genome is mediated through activation of a virally encoded transcription factor, Z (BZLF1). We have shown that the Z gene product, which binds to AP-1 sites as a homodimer and has sequence similarity to c-Fos, can efficiently activate the EBV early promoter, BMRF1, in certain cell types (i.e., HeLa cells) but not others (i.e., Jurkat cells). Here we demonstrate that the c-myb proto-oncogene product, which is itself a DNA-binding protein and transcriptional transactivator, can interact synergistically with Z in activating the BMRF1 promoter in Jurkat cells (a T-cell line) or Raji cells (an EBV-positive B-cell), whereas the c-myb gene product by itself has little effect. The simian virus 40 early promoter is also synergistically activated by the Z/c-myb combination. Synergistic transactivation of the BMRF1 promoter by the Z/c-myb combination appears to involve direct binding by the Z protein but not the c-myb protein. A 30-bp sequence in the BMRF1 promoter which contains a Z binding site (a consensus AP-1 site) is sufficient to transfer high-level lymphoid-specific responsiveness to the Z/c-myb combination to a heterologous promoter. That the c-myb oncogene product can interact synergistically with an EBV-encoded member of the leucine zipper protein family suggests c-myb is likely to engage in similar interactions with cellularly encoded transcription factors.
Mol Cell Biol 1992 Jan
PMID:The cellular oncogene c-myb can interact synergistically with the Epstein-Barr virus BZLF1 transactivator in lymphoid cells. 130 87

Gene expression of visna virus is highly restricted in monocytes, but is induced when monocytes differentiate into macrophages. A previous study on differential regulation of visna virus gene expression revealed that a specific AP-1 site in the long terminal repeat of the viral DNA is required for phorbol-ester-induced gene expression in macrophages (Gabuzda, Hess, Small, and Clements, Mol. Cell. Biol., 9, 2728-2733). In the present investigation, we examined the association of two DNA binding proteins, the proto-oncogene proteins FOS and JUN, with this AP-1 site in the visna virus LTR. We demonstrated that the concentrations of these two proteins and their mRNAs increased in U937 cells after phorbol ester induction. Furthermore, the binding of cellular proteins from the U937 nuclear extracts to this AP-1 site was significantly decreased in the presence of antibodies to JUN and FOS. In vitro-translated JUN protein also binds to this AP-1 sequence, and this binding is enhanced by the FOS protein. These results indicate that JUN and FOS are directly involved in the differential regulation of visna virus gene expression.
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PMID:Involvement of FOS and JUN in the activation of visna virus gene expression in macrophages through an AP-1 site in the viral LTR. 132 22

Activation of either muscarinic cholinergic or thrombin receptors increases phosphoinositide turnover, Ca2+ mobilization, and redistribution of protein kinase C and induces rapid transient increases in c-fos mRNA and c-jun mRNA in 1321N1 cells. To determine whether the increases in c-fos and c-jun mRNA induced by carbachol and thrombin are sufficient to stimulate AP-1-mediated transactivation, 1321N1 cells were transfected with a reporter carrying two copies of the tetradecanoyl phorbol acetate response element and the firefly luciferase gene. Thrombin was significantly more effective than carbachol at stimulating AP-1-mediated transactivation. To identify the factors underlying the difference in AP-1 activity induced by carbachol and thrombin, members of the fos and jun families which encode components of AP-1 were examined. Carbachol and thrombin have similar effects on expression of c-fos, fosB, fra-2, junB, and junD, both acutely and over a 24-h time course. However, whereas carbachol leads only to transient induction of c-jun (maximal at 0.5 h), thrombin induces a biphasic increase in c-jun mRNA--an initial peak at 0.5 h and a second, more-prolonged increase at 12 h. Thrombin but not carbachol also induces a late increase in fra-1 mRNA, which peaks at 12 h. The secondary increase in c-jun mRNA is associated with marked increases in c-Jun protein levels and AP-1 DNA-binding activity. The late induction of c-jun and fra-1 mRNA can be prevented by adding the antagonist hirudin 30 min after thrombin, which results in loss of thrombin-stimulated increases in c-Jun protein, AP-1 DNA-binding activity, and AP-1-mediated transactivation. These findings suggest that rapid and transient conduction of c-fos and c-jun mRNA is insufficient to induce prominent changes in gene transcription, while the sustained increase in c-jun mRNA and perhaps the late induction of fra-1 mRNA are required for generation of AP-1 DNA-binding activity and transactivation through AP-1.
Mol Cell Biol 1992 Oct
PMID:Biphasic increase in c-jun mRNA is required for induction of AP-1-mediated gene transcription: differential effects of muscarinic and thrombin receptor activation. 132 61

The linkage between the transmembrane signal transduction system utilized by endothelin and alterations in gene expression has been investigated in C6 glioma cells. Treatment of C6 cells with endothelin-1 caused a rapid and transient 5-fold increase in c-fos and c-jun mRNA levels, followed by a decrease at 4 h. Dose-response studies indicated that 1 nM endothelin-1 caused half-maximal induction of c-fos mRNA 0.5 h after treatment and that maximal induction was elicited with a concentration of 10 nM. Actinomycin D totally abolished the rapid increase in c-fos mRNA caused by endothelin, indicating that the effect is at the transcriptional level. Endothelin-1 caused a decrease in proenkephalin mRNA to 50% of control levels at 4 h after treatment and had no effect on histone H4 mRNA over a 24 h period that was examined. These data indicate that receptor binding of endothelin-1 leads to rapid changes in the expression of immediate-early response genes which may cause more prolonged changes in the expression of AP-1 and/or CREB target genes in the nervous system.
Brain Res Mol Brain Res 1992 Jul
PMID:Stimulation of c-fos and c-jun gene expression and down-regulation of proenkephalin gene expression in C6 glioma cells by endothelin-1. 133 50

The expression of AP-1 transcription factors was assessed in the dopamine-depleted rat striatum over a 1 week period of repeated apomorphine injections. A single injection of apomorphine increased the expression of a 35 kDa Fos-related antigen and Jun proteins and their expression continued to increase until day 3 of repeated apomorphine treatment in dopamine-depleted striata. Apomorphine induces AP-1 transcription factors which may be involved in modulating gene expression in the striatum.
Brain Res Mol Brain Res 1992 Sep
PMID:Apomorphine induction of AP-1 DNA binding in the rat striatum after dopamine depletion. 133 62

We previously studied the transcriptional mechanisms involved in expression of the murine nerve growth factor (NGF) gene. To investigate the regulation of transcription of the human NGF gene, the promoter region was cloned. The nucleotide sequences of the human and mouse genes are greater than 90% similar near their promoters. The cloned human promoter was transcriptionally active in mouse L929 fibroblasts. 5' Deletion analyses indicated that the -85 to -45 region stimulates basal transcription 6-fold. This segment is greater than 80% identical in human and mouse genes except for an AP-1 consensus sequence found only in the human gene. A second AP-1 consensus sequence at +34, previously shown to function as a regulatory element in the mouse gene, is identical in both genes. Gel shift analyses of L929 cell extracts revealed binding of protein to oligonucleotide probes spanning each of the two AP-1 consensus sequences of the human gene. The gel shift patterns differed, suggesting interaction of different proteins with the two probes. Our results demonstrate that the human NGF gene promoter is transcriptionally active in mouse fibroblasts, and implicate an upstream region in basal transcription.
Brain Res Mol Brain Res 1992 Sep
PMID:The human nerve growth factor gene: structure of the promoter region and expression in L929 fibroblasts. 133 71

In order to identify potential regulatory elements of the human mid-sized (M) neurofilament (NF) gene we preformed DNase I footprinting, gel mobility shift assays and methylation interference studies with probes from the NF(M) immediate 5' flanking region. These studies identified multiple sites for DNA-binding proteins including four Sp1 sites, and single sites each for members of the NF-1 and AP-1 families of DNA binding proteins. In addition a binding site within a pyrimidine tract likely binds a novel DNA-binding protein which also interacts with the human NF(H) gene promoter. Factors that bind to these sites are found in both neural and non-neural cells suggesting that the NF(M) promoter may not contain tissue specific regulatory signals. In transient assays, addition of these binding sites to an NF(M) minimal promoter containing only a TATA box lead to a greater than 40-fold activation of transcription over background. Progressive 5' deletions reduced expression in a step wise manner suggesting that all the factors likely act synergistically as positive regulators of transcription.
Brain Res Mol Brain Res 1992 Sep
PMID:Multiple nuclear factors interact with the promoter of the human neurofilament M gene. 133 73

c-Fos and c-jun are immediate early proto-oncogenes encoding proteins for the heterodimer AP-1, a DNA binding complex which regulates gene transcription. In order to investigate the presence and potential gonadotropin regulation of mRNAs for these proto-oncogenes in rat granulosa cells, we used Northern blotting of total RNA from cultured cells. Granulosa cells obtained from diethylstilbestrol (DES)-treated weanling rats were challenged with follicle-stimulating hormone (FSH), luteinizing hormone (LH), human chorionic gonadotropin (hCG), dibutyryl cAMP ((Bu)2cAMP) or tetradecanoyl-13-phorbol acetate (TPA) either 2.5 h after cell isolation (day 0) or following a 2-day pretreatment with FSH (day 2). Freshly isolated cells treated with FSH exhibited 4-fold and 3-fold increases in c-fos and c-jun mRNAs, respectively, within 30 min. Two hours after FSH treatment, both c-fos and c-jun message levels diminished to near control levels. Granulosa cells pretreated for 2 days with FSH, then re-challenged with FSH, showed similar increases in both c-fos and c-jun messages. These effects were dose- and time-dependent on both day 0 and day 2. Likewise, (Bu)2cAMP also increased c-fos and c-jun mRNAs in a time- and dose-dependent manner on both day 0 and day 2. In contrast, LH or hCG minimally increased c-fos and c-jun mRNAs on day 0, but on day 2, both hormones markedly increased message levels in a manner similar to that seen with FSH. Analogous effects were observed with TPA which minimally stimulated c-fos and c-jun mRNAs on day 0, but markedly increased these messages on day 2. These studies demonstrate that c-fos and c-jun mRNAs can be induced in cultured rat granulosa cells by acute gonadotropin, (Bu)2cAMP or phorbol ester treatment and suggest that these immediate early proto-oncogenes may play a role in granulosa cell function.
Mol Cell Endocrinol 1992 Dec
PMID:Gonadotropin regulation of c-fos and c-jun messenger ribonucleic acids in cultured rat granulosa cells. 133 29

In both mouse sarcoma 180 and human KB cells selected for the multiple drug resistance (MDR) phenotype, there is an elevation in the steady state mRNA level of c-fos. There is no detectable gene amplification for c-fos, nor is there any significant change in the rate of mRNA transcription or degradation, suggesting that other factors are responsible for the increased expression level in resistance. Cells selected for resistance to methotrexate, a drug not in the MDR group, do not have an increase in c-fos mRNA expression. When drug-sensitive cells are exposed for 30 min to an ED50 concentration of vinblastine, Adriamycin, colchicine, or VP-16, but not to methotrexate or cisplatin, there is a 3-6-fold induction in the level of c-fos message. Because the former drugs are members of the MDR class and the latter are not, the results are consistent with the hypothesis that induction of c-fos by low levels of cytotoxic drugs may be an early event in the acquisition of the MDR phenotype. If this were the case, then c-fos would be expected to act in concert with c-jun to control transcription by binding to a specific DNA regulatory site. Consistent with this explanation is the existence of an AP-1 sequence in the promotor region for the P-glycoprotein gene (mdr1), as well as the fact that c-jun is also overexpressed in MDR cells.
Mol Pharmacol 1992 Jul
PMID:Expression of c-fos in human and murine multidrug-resistant cells. 135 51

Several endocrine hormones which influence liver metabolism are known to increase in activity during the acute phase of injury or inflammation. We determined whether these hormones have the potential to influence acute-phase protein production in human and rat hepatoma cells. Catecholamines, glucagon, growth hormone, triiodothyronine, and cyclic nucleotides individually or in combination did not modulate the basal or the interleukin-1 (IL-1)-, IL-6-, and dexamethasone-stimulated levels of acute-phase plasma proteins. Insulin, however, was found to be a rapid, nonspecific, and dose-dependent inhibitor of the cytokine and glucocorticoid stimulation of acute-phase protein gene expression and to exert its effect at the transcriptional level. The insulin inhibition applied to all cytokines tested but to various degrees, depending upon the particular acute-phase gene. Insulin resulted in an early and prominent increase in the transcription of genes encoding the AP-1 components of JunA, JunB, and c-Fos, as has been observed for other growth factors. However, the effect of insulin on C/EBP beta was unexpected and paradoxical: while insulin completely inhibited the transcriptional activation of the C/EBP beta gene in cytokine- and dexamethasone-treated cells, the level of cytoplasmic C/EBP beta RNA was elevated. Quantitation of C/EBP beta mRNA by Northern (RNA) blot analysis and of C/EBP beta DNA binding activity by Southwestern (DNA-protein) blot analysis showed that insulin, when combined with cytokines and dexamethasone, stimulated both the mRNA and DNA binding activity by a factor of 1.6 compared with that of cells treated with cytokines and dexamethasone alone. Transient transfection of H-35 and HepG2 cells with a chloramphenicol acetyltransferase (CAT) gene expression vector containing the C/EBP beta response element also resulted in a 1.5-fold increase of C/EBP beta-mediated transcription in insulin-treated cells. Transfection of CAT gene constructs containing increasing lengths of heptaglobin gene 5' flanking sequences indicated that insulin inhibition of IL-6 stimulation required the presence of the region from -4100 to -1030. These results suggest that insulin has the potential to control the transcription of acute-phase genes by at least two separate mechanisms.
Mol Cell Biol 1992 Apr
PMID:Insulin is a prominent modulator of the cytokine-stimulated expression of acute-phase plasma protein genes. 137 89


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