Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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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

Chemically induced differentiation of Friend murine erythroleukemia cells (F-MELC) is a multistep process with a latent period of about 12 h preceding irreversible commitment to terminal maturation. To gain understanding of the early genetic response of F-MELC to the dimethyl sulfoxide (DMSO) inducer of F-MELC differentiation, we have investigated by Northern blot analysis the expression of fos and jun family genes that encode components of the transcription factor AP-1 complex. Our results show that c-jun mRNA is not detected at any time in untreated and DMSO-treated F-MELC. In contrast, DMSO-induced differentiation of F-MELC is associated with an early and transient induction of c-fos and junB mRNAs by 2 to 8 h treatment while in presence of dexamethasone, an inhibitor of F-MELC commitment, c-fos mRNA is not detected and junB mRNA remains at basal levels. junD mRNA is detected at low levels in untreated F-MELC and remains unchanged during DMSO treatment. Furthermore, DMSO treatment in a F-MELC cell line resistant to DMSO-differentiation does not result in an early induction of c-fos and junB mRNAs. Taken together, these results indicate that the DMSO-induced F-MELC differentiation is accompanied by an early co-induction of c-fos and junB during the latent period preceding the commitment to erythroid maturation.
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PMID:Co-induction of c-fos and junB during the latent period preceding commitment of Friend erythroleukemia cells to differentiation. 151 4

The c-myb protooncogene, which is preferentially expressed in hematopoietic cells at the G1/S boundary of the cell cycle, encodes a transcriptional activator that functions via DNA binding. The regulatory mechanisms governing this specific pattern of expression are not fully understood, although human c-myb expression appears to be positively autoregulated via myb-binding sites in the 5'-flanking region of the c-myb gene (Nicolaides, N. C., Gualdi, R., Casadevall, C., Manzella, L., and Calabretta, B. (1991) Mol. Cell. Biol. 11, 6166-6176). To determine the contribution of other transcription regulators such as JUN family members in the control of c-myb expression, transient expression assays were carried out which revealed a 6- to a 15-fold enhancement by c-Jun and JunD, but not JunB, in chloramphenicol acetyltransferase reporter gene expression driven by different segments of the human c-myb 5'-flanking region. An Ap1-like element located at nucleotide -149 from the c-myb initiation site appears to be required for this transactivation upon binding to a nuclear protein complex containing c-Jun and JunD, since site-directed mutations of this Ap1-like element abolished c-Jun and JunD binding and transactivation. Exposure of phytohemagglutinin-stimulated peripheral blood mononuclear cells to c-jun and junD antisense oligodeoxynucleotides resulted in a 46 and 43% inhibition of T-lymphocyte proliferation that was accompanied by a decrease in c-myb mRNA levels as compared with sense-treated cultures. Because T-lymphocytes induced to proliferate express c-jun and junD before c-myb, these data suggest a mechanism whereby c-Jun and JunD contribute to the transcriptional activation of c-myb that, in turn, is maintained at the G1/S transition and during S phase by positive autoregulation.
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PMID:The Jun family members, c-Jun and JunD, transactivate the human c-myb promoter via an Ap1-like element. 152 86

Treatment of sensitive EL4 mouse thymoma cells with phorbol esters causes growth inhibition, adherence to substrate and production of several lymphokines including Interleukin 2. Resistant cells lack all of these responses. Since production of Interleukin 2 mRNA is dependent on protein synthesis, and the Interleukin 2 gene has a phorbol ester responsive element, we examined both cell lines for expression of the various Jun and Fos species which bind to this element. Phorbol ester induced c-fos, jun-B, and jun-D RNAs within 20 min in both cell lines. Fos-B was similarly induced in sensitive cells but induction was delayed and greatly enhanced in resistant cells. C-jun RNA induction was detected only in sensitive cells. Western analysis confirmed the induction of c-Jun and a Fos-related protein in sensitive cells only. Southern analysis indicated that both cell lines contain c-jun and fra-1 genes. These results suggest that defective induction of c-Jun and/or Fos-related proteins may contribute to the absence of phorbol ester-induced lymphokine production in resistant EL4 cells.
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PMID:Defective induction of Jun and Fos-related proteins in phorbol ester-resistant EL4 mouse thymoma cells. 171 62

The transcription factor AP-1 is phorbol ester-regulated and, as such, is considered to be a nuclear target of the signal transduction pathway involving protein kinase C. AP-1 is constituted by the various products of the jun and fos gene family members. These genes belong to the early response class and are inducible in different ways by growth factors, phorbol esters and depolarization. We studied the transcript distribution of c-jun, junB and junD in the rat brain. Our results show that the transcripts for these three genes are differentially distributed in various neuronal tissues. We also provide evidence for developmentally regulated expression of jun genes in post-natal brain. The spatiotemporal pattern of expression of c-jun, junB and junD offers clues to the understanding of the links between gene regulation and neuronal processes.
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PMID:Differential expression of the jun family members in rat brain. 171 62

We have investigated the role of the two AP-1 sites, located at approximately -150 and -180 bp relative to the transcription start site, in induction of the IL-2 promoter through the TCR/CD3 complex. We show that only the proximal (-150 bp) AP-1 site is functional in vitro, as judged by its ability to bind nuclear proteins from T cells stimulated with Ag or anti-CD3 epsilon. The inducible nuclear proteins binding to this site have the characteristics of AP-1, as judged by their kinetics of induction, the ability to compete and be competed efficiently by a metallothionein AP-1 site oligonucleotide, and their reaction with antibodies to Fos and Jun proteins. Mutations in the proximal AP-1 site greatly diminish or abrogate induction of the IL-2 promoter, indicating that the site is also functional in vivo. Although the distal (-180 bp) AP-1 site is incapable of direct binding to nuclear proteins from activated T cells, a mutation in this site diminishes IL-2 promoter induction, suggesting that this site may also be functional in vivo. Cotransfection of a 5' IL-2-chloramphenicol acetyltransferase plasmid with c-Fos and/or c-Jun enhances the induction of IL-2-chloramphenicol acetyltransferase activity, confirming that the IL-2 promoter contains a functional AP-1 site. Both AP-1 sites may be targets for c-Fos action, as inferred from the results of experiments in which c-Fos was cotransfected with internal deletion mutants of the IL-2 promoter lacking either AP-1 site. Northern analysis indicates that mRNAs for at least six members of the Fos/Jun family (c-fos, fosB, fra-1, c-jun, junB, and junD) are expressed in activated Ar-5 cells; thus the AP-1 sites of the IL-2 promoter may bind different dimeric Fos/Jun complexes at different times after T cell activation, perhaps mediating both positive and negative regulation of the IL-2 promoter.
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PMID:Analysis of the AP-1 sites in the IL-2 promoter. 173 37

The genes of the Jun family encode components of the TPA-inducible transcription factor AP-1. These genes are induced by a wide variety of extracellular stimuli, such as growth factors, phorbol esters and activators of protein kinase A. We have previously shown that the adenovirus type 5 E1A protein (E1A5) induces c-jun and junB expression in a number of different cell types. In this paper we show that the third member of the Jun family, junD, is also strongly induced by E1A5. Multiple sequences in the junB and junD promoters are responsible for the effects of E1A5. By contrast, adenovirus type 12 E1A (E1A12), like retinoic acid (RA), strongly induces c-jun expression, while expression of junB and junD is not altered. Interestingly, E1A12 expression leads to complete differentiation of P19 EC cells, comparable to the effect of RA on these cells, while E1A5-expressing cells are only partially differentiated.
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PMID:Differential regulation of JunB and JunD by adenovirus type 5 and 12 E1A proteins. 183 51

We have isolated and characterized the chicken junD gene. It does not contain an intron; its upstream regulatory sequences lack the AP-1-binding site seen in c-jun but include two CRE elements. Downstream untranslated sequences do not show the destabilizing signal ATTTA. The amino acid sequence of the chicken JunD protein is closely related to that of mouse JunD in the dimerization and DNA contact surfaces of the carboxy-terminal region; additional homologies to mouse JunD are seen in acidic and amphipathic amino-terminal domains. Chicken JunD contains stretches of oligoglycines, alanines and prolines, possibly acting as hinges that connect functionally distinct domains of the protein. Chicken junD is broadly expressed at low basal levels in differentiated tissues and at somewhat higher levels in cultured fibroblasts. The cDNA clone of junD was transcribed and translated in vitro. The resulting JunD protein migrates in between 40 and 50 kDa in an SDS gel and can be precipitated with an antibody prepared against a polypeptide consisting of the carboxy-terminal 100 amino acids of mouse c-Jun.
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PMID:The chicken junD gene and its product. 192 29

The coding sequences of murine c-jun, junB, or junD, which code for proteins with practically identical dimerization and DNA binding properties, were introduced into a nondefective retroviral vector, and the phenotype of primary avian fibroblasts chronically infected with each of these viruses was studied. Cells expressing c-jun grew in low-serum medium and developed into colonies in agar, two properties characteristic of in vitro transformation. Cells expressing junB grew in agar, with a reduced efficiency as compared to c-jun, but did not grow in low-serum medium. Finally, no effect of junD expression on cell growth was observed. These different phenotypes suggest that these three closely related transcription factors play distinct roles during normal cell growth. Analysis of c-jun deletion mutants and of c-jun/junB and c-jun/junD chimeric genes showed that the N-terminal portion (amino acids 2-168) of the c-Jun protein that is involved in transcriptional activation is required for efficient transformation. On the contrary, cells expressing a truncated mouse c-Jun lacking this N-terminal domain grew slower than normal embryo fibroblasts. The reduced growth rate may be related to the finding that expression of the intact or the truncated mouse c-jun repressed the endogenous avian c-Jun homologue, suggesting that functional c-Jun product is required for normal cell growth.
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PMID:Overexpression of c-jun, junB, or junD affects cell growth differently. 192 49

Fra-2, one of the Fos-related antigens, is promptly expressed after the growth stimulation of fibroblasts, but its induction peak is later than that of c-Fos. In this report, we examined biochemical properties of Fra-2 and compared them with those of two other Fos family proteins, c-Fos and Fra-1. Like c-Fos and Fra-1, Fra-2 formed stable heterodimers with c-Jun, JunB or JunD in vitro and all these complexes had specific DNA-binding activity to AP-1-binding sites (AP-1 sites) or related sequences. When transiently introduced into a mouse embryonic carcinoma cell line, F9, with reporter genes containing the AP-1 site from the collagenase gene, fra-2 plus c-jun suppressed the transactivation by c-jun alone. This property of Fra-2 is in clear contrast to that of c-Fos, which stimulates the transcriptional activity of c-Jun by forming a stable heterodimer. Analysis of chimeric proteins between c-Fos and Fra-2 indicated that this difference is mainly attributable to their C terminal-half regions. Interestingly, this suppressive effect of Fra-2 was not observed in the combination with JunD: fra-2 plus junD, like c-fos plus junD, had higher transcriptional activity than junD alone. Fra-1 showed essentially the same transcriptional regulatory properties as Fra-2. These differential properties greatly expand the potential range of regulatory functions of the Fos family proteins.
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PMID:Difference in transcriptional regulatory function between c-Fos and Fra-2. 194 31


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