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Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hepatic expression of the alpha-2u-globulin gene family is controlled by a variety of hormones including steroids, growth hormone and insulin. The mechanisms by which these hormones affect alpha 2u-globulin expression are only partially understood. Recently we isolated and characterized clone RAP 01, an alpha 2u-globulin gene expressed in the liver. In preliminary experiments we noted that partial hepatectomy, a procedure which results in a sharp rise in the level of the oncoproteins c-Fos and c-Jun, also causes a transient induction of the messenger RNA corresponding to clone RAP 01. Using the DNAseI footprinting technique we were able to show that this clone contains a TPA (phorbol 12-myristate 13-acetate)-responsive element (TRE) in its first intron. This element (denoted as element X) is identical to the consensus AP-1 binding site (TGACTCAG) and is protected by rat liver nuclear extracts as well as by purified c-Jun. Gel retardation experiments show that an oligonucleotide containing the TRE consensus sequence competes for binding of liver nuclear proteins to element X and that antibodies directed against the M2 peptide of the mouse Fos protein or the PEP-2 peptide of Jun prevent the formation of specific complexes with the same element. Moreover, element X functions as a TRE in transfected BWTG3 hepatoma cells treated with TPA. Co-transfection with fos and jun expression vectors mimics the effects of TPA suggesting that AP-1 is in fact the mediator of the observed response. It is concluded that the first intron of RAP 01 contains a functional Fos-Jun element.
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PMID:A Fos-Jun element in the first intron of an alpha 2u-globulin gene. 750 7

The hepatitis B virus (HBV) X protein (pX) is capable of activating transcription regulated by viral and cellular promoters containing binding sites for different transcription factors, including AP1. In this study we have analyzed the mechanisms of AP1 induction by pX. The hepatitis B virus transactivator was able to activate TRE (12-O-tetradecanoylphorbol-13-acetate response element)-directed transcription in different cell lines, including HepG2, HeLa, CV1, and PLC/PRF/5 cells. pX-induced AP1 activation in HepG2 cells was associated with an increase in the DNA-binding activity of c-Jun/c-Fos heterodimers, which was not dependent either on an increase in the overall amount of c-Fos and c-Jun proteins in the cells or on formation of dimers between pX and the two proteins, thus suggesting the involvement of posttranslational modifications of the transcription factor. The observation that the overexpression of c-Jun and c-Fos in the cells results in a strong augmentation of the effect of pX on TRE-directed transcription is additional evidence indicating the involvement of posttranscriptional modifications of c-Jun/c-Fos heterodimers. The increased AP1 binding observed in the presence of pX was unaffected by the protein kinase C inhibitors calphostin C and sphingosine and by the protein kinase A inhibitor HA1004, while it was almost completely blocked by staurosporine, a potent and nonspecific protein kinase inhibitor, suggesting that protein kinase C- and A-independent phosphorylation events might play a role in the phenomenon. The ability of pX also to increase TRE-directed transcription in cell lines in which AP1-binding activity is not increased (i.e., HeLa, CV1, and PLC/PRF/5 cells) suggests that pX can activate canonical TRE sites by different mechanisms as well.
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PMID:Induction of the DNA-binding activity of c-jun/c-fos heterodimers by the hepatitis B virus transactivator pX. 750 9

In differentiated 3T3-F442A adipocytes, insulin stimulated rapid and transient phosphorylation of c-Jun. Insulin also stimulated phosphorylation of c-Fos and several Fos-related proteins (pp72, pp45, and pp39) as indicated by precipitation with anti-c-Fos antibody following exposure to denaturating conditions. Phosphorylation of c-Fos was stimulated by 7-fold by 60 min, while phosphorylation of Fos-related proteins reached maxima of 3.5-5.5-fold at 15 to 60 min. The increase in phosphorylated c-Fos was due to an increase in both c-Fos protein and the stoichiometry of c-Fos phosphorylation, and was not observed in c-fos (-/-) cells. Additionally, insulin stimulated phosphorylation of a protein with molecular mass of approximately 82 kDa on tyrosine residues by 2.5-fold within 30 min; this protein appeared to be immunologically related to c-Fos. These increases in the phosphorylation of AP-1 transcription factors correlated with a > 5-fold stimulation of expression of a 12-O-tetradecanoylphorbol-13-acetate-responsive element-chloramphenicol acetyltransferase reporter gene transiently transfected into 3T3-F442A cells. These results indicate that insulin stimulates the phosphorylation of AP-1 transcription factors and several Fos-related proteins on serine and tyrosine residues. This is associated with changes in AP-1-mediated gene expression in vivo, suggesting that AP-1 phosphorylation by insulin plays a role in insulin-regulated gene expression.
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PMID:Insulin stimulates phosphorylation of c-Jun, c-Fos, and Fos-related proteins in cultured adipocytes. 751 56

In KB epidermoid cells, we previously showed that interleukin-1 alpha (IL-1) and various mitogens activate the mitogen-activated protein (MAP) kinases ERK1 and ERK2, which phosphorylate both myelin basic protein (MBP) and a peptide containing Thr669 of the epidermal growth factor receptor. In cell-free extracts made from gingival fibroblasts treated with platelet-derived growth factor or HepG2 hepatoma cells stimulated with phorbol myristate acetate, MBP and Thr669 kinase were both elevated 4-fold, and ERK1 and ERK2 were tyrosine-phosphorylated. In these cells IL-1 activated a kinase(s) that phosphorylated Thr669 peptide but not MBP and failed to cause tyrosine phosphorylation of ERK1/ERK2. Ceramide has been proposed as an intracellular mediator of IL-1 action, but C2-ceramide or sphingosine stimulated predominantly MBP-specific kinase activity in fibroblasts and had no effect in HepG2 cells. p54 MAP kinase (also called stress-activated protein kinase) is a c-Jun kinase first isolated from livers of cycloheximide-treated rats. After IL-1 stimulation, immunoprecipitates of lysates made from all three cell types with specific anti-p54 MAP kinase serum contained Thr669 and c-Jun phosphorylating activity, whereas precipitates from unstimulated cells contained no detectable p54 kinase activity. The major peak of IL-1-stimulated HepG2 Thr669 kinase activity co-chromatographed on Mono Q and phenyl-Superose with immunodetectable p54 MAP kinase. IL-1 did not cause p21ras activation in any cell type. Induction of Thr 669 kinase activity was not abrogated by elevation of cAMP levels, which has been shown to interfere with the activation of Raf-1. We could not detect MAP kinase kinase phosphorylating activity in unfractionated lysates made from IL-1-stimulated fibroblasts or HepG2 cells. KB cells contained a small amount of this activity, but it was not precipitated with an anti-Raf-1 antibody. We conclude that most of the IL-1-activated Thr669 kinase activity in fibroblasts and HepG2 cells, and a portion in KB cells, is due to p54 MAP kinase and that its activation is Ras-, Raf-, and MAP kinase kinase-independent.
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PMID:Interleukin-1 activates p54 mitogen-activated protein (MAP) kinase/stress-activated protein kinase by a pathway that is independent of p21ras, Raf-1, and MAP kinase kinase. 752 98

Human CD45RA+ ('naive') and CD45RO+ ('memory') CD4+ T cells were compared with respect to their sensitivity to dexamethasone (DEX). In three different activation pathways, i.e. (i) immobilized anti-CD3, (ii) immobilized anti-CD3 plus soluble anti-CD28 and (iii) soluble anti-CD2 plus soluble anti-CD28, naive CD4+ T cells appeared more sensitive to DEX than memory CD4+ T cells. In the anti-CD3 system this difference in sensitivity was apparent at a suboptimal DEX concentration. Addition of anti-CD28 rendered the cells largely insensitive to DEX, indicating that the CD28 pathway is less dependent of the DEX-sensitive transcription factor AP-1. However, the alternative pathway of T cell activation through CD2/CD28 triggering was highly sensitive to DEX when naive cells were studied; in the case of memory cells, at least a 10-fold higher DEX concentration was needed to achieve a comparable inhibition. The strong inhibitory effect of DEX on naive CD4+ T cells stimulated via the alternative pathway was completely abrogated by activation of protein kinase C (PKC) with phorbol myristate acetate. Our data suggest that at least two different mechanisms contribute to DEX resistance, i.e. CD28 triggering and PKC activation, which may occur more effectively in memory cells making them less sensitive to DEX.
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PMID:Differential sensitivity of human naive and memory CD4+ T cells for dexamethasone. 754 86

Curcumin is a potent inhibitor of tumor promotion, and was shown previously to inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced AP-1 activity. The c-Fos protein is inducible by TPA and thus is associated with c-Jun to result in an increased AP-1 activity in mouse fibroblast cells. We therefore hypothesized that c-Fos may be one of the targets of curcumin action. In the present study, the effects of curcumin on TPA-induced c-fos mRNA and protein levels were determined by RNA hybridization and western blot analysis, respectively. Curcumin decreases the TPA-induced nuclear abundance of c-Fos protein in spite of the slight super-induction of c-fos mRNA. Upon TPA stimulation, the amount of c-Fos in the quiescent cells increases and reaches maximum at 30 min, and then progressively disappears over a period of 60 min. However, the c-Fos protein seems susceptible to rapid degradation by 45 min if NIH 3T3 cells were treated with TPA in the presence of curcumin. The curcumin-induced hyperphosphorylated forms of c-Fos proteins are significantly more unstable; they entirely disappeared within 40 min after incubation at 37 degrees C. These findings prompted us to suggest that the decrease of c-Fos protein could account for the repressed in vitro DNA binding probably by reducing the Jun/Fos complex formation.
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PMID:A labile hyperphosphorylated c-Fos protein is induced in mouse fibroblast cells treated with a combination of phorbol ester and anti-tumor promoter curcumin. 755 96

Ceramide has emerged as a novel lipid mediator in cell proliferation, differentiation, and apoptosis. In this work, we demonstrate that the levels of c-jun mRNA, c-Jun protein, and DNA binding activity of a nuclear transcription factor AP-1 to 12-o-tetradecanoylphorbol 13-acetate responsive elements all increased following treatment with the cell-permeable ceramide, N-acetylsphingosine in human leukemia HL-60 cells. N-Acetylsphingosine (1-10 microM) increased the levels of c-jun mRNA in a dose-dependent manner, and maximal expression was achieved 1 h after treatment. Increase of c-jun expression treated with 5 microM N-acetyldihydrosphingosine, which could not induce apoptosis, was one third of that with 5 microM N-acetylsphingosine. Ceramide-induced growth inhibition and DNA fragmentation were both prevented by treatment with curcumin, 1,7-bis[4-hydroxy-3-methoxy-phenyl]-1,6-heptadiene-3,5-dione (an inhibitor of AP-1 activation), or antisense oligonucleotides for c-jun. These results suggest that the transcription factor AP-1 is critical for apoptosis in HL-60 cells and that an intracellular sphingolipid mediator, ceramide, modulates a signal transduction inducing apoptosis through AP-1 activation.
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PMID:Requirement of AP-1 for ceramide-induced apoptosis in human leukemia HL-60 cells. 759 95

We have previously reported that the promoter region of the mouse interleukin-5 (IL-5) gene, extending from a nucleotide position about -1,200 to +33 relative to the transcription initiation site, can mediate transcriptional stimulation by phorbol 12-myristate 13-acetate and dibutyryl cAMP (Bt2cAMP) in mouse thymoma EL-4 cells. Here, we describe identification of four cis-regulatory elements necessary for full activity of the IL-5 promoter, using deletion and mutation analyses. We designated these elements as IL-5A (-948 approximately -933), IL-5P (-117 approximately -92), IL-5C (-74 approximately -56), and IL-5CLE0 (-55 approximately -38). We found that IL-5P bears homology to the binding site for the nuclear factor of activated T cells (NF-AT) and interacted with protein factors in nuclear extracts prepared from EL-4 cells stimulated with phorbol 12-myristate 13-acetate and Bt2cAMP (designated NFIL-5P). NFIL-5P complex was inhibited in the presence of an excess NF-AT and AP1 oligonucleotides and super-shifted by antisera raised against NF-ATp, c-Fos, and c-Jun. It thus seems likely that an NF-AT-related factor is involved in the regulation of IL-5 gene transcription.
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PMID:Definition of cis-regulatory elements of the mouse interleukin-5 gene promoter. Involvement of nuclear factor of activated T cell-related factors in interleukin-5 expression. 761 60

Facial motoneurons respond to peripheral transection of the facial nerve with a number of molecular changes. In order to obtain insight into the transcriptional mechanisms underlying the changes induced by axotomy, the expression of a number of immediate early genes was investigated after facial nerve lesion in the rat. Some immediate early genes (such as c-fos, c-jun or jun B) are known to encode transcription factors that bind to DNA at sites that regulate gene expression and they could therefore contribute to long-term changes in motoneurons. Northern blot analysis of RNA extracted from the facial nucleus from postoperative intervals covering hours and days revealed that axotomy results in a unique pattern of immediate early gene induction in the facial nucleus. c-Jun, jun B and 12-O-tetradecanoylphorbol-13-acetate-induced sequence (TIS) 11 messenger RNA, also present in low amounts in the unoperated nucleus, were strongly induced in a long-term fashion after nerve injury. Increased levels of these messenger RNAs were first detectable at 5 h, reaching a maximum (300-500% compared to control) within 24 h followed by a gradual decline during the following week. Elevated levels were maintained at least up to eleven days compared to the unoperated side. On the other hand, c-fos messenger RNA was neither expressed in the unoperated nucleus, nor was c-fos messenger RNA induced by axotomy at any of the time-points studied. Another member of the TIS family of immediate early genes TIS 7 (PC4), however, was detectable at low levels in normal facial nucleus, but its expression was unaffected by lesion. The three axotomy-induced messenger RNAs, c-jun, jun B and TIS 11, were all localized in the facial motoneurons by in situ hybridization histochemistry indicating that their induction occurs as part of the retrograde reaction of the motoneurons in response to lesion. These data suggest that c-jun, jun B and TIS 11 may play a role in triggering the regeneration programme of motoneurons.
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PMID:Differential expression of immediate early genes after transection of the facial nerve. 768 1

Glucocorticosteroids have a wide variety of effects which result in the long-term dampening of inflammatory responses. An important site of steroid action may be on the control of the activator protein-1 (AP-1) binding to deoxyribonucleic acid (DNA). AP-1 is a proinflammatory transcription factor composed of a heterodimer of Fos and Jun proto-oncogenes, which can be induced by phorbol esters and various cytokines. We have examined the hypothesis that dexamethasone may inhibit inflammation via an effect on AP-1 activation in human lung tissue. The effect of dexamethasone on the phorbol ester and cytokine activation of AP-1 and its monomers was examined in human lung tissue obtained from transplantation donors. AP-1 activation was measured by its ability to bind DNA, its localization in the nucleus by Western blotting, and the levels of fos and jun messenger ribonucleic acids (mRNAs) using Northern blotting. The phorbol ester, phorbol myristate acetate (PMA), caused a significant 2-3 fold increase in AP-1 DNA binding, which was sustained for 24 h and completely attenuated by co-incubation with dexamethasone. Dexamethasone alone caused a 40% decrease in AP-1 DNA binding. Dexamethasone modulated the expression of both c-jun and c-fos mRNA and produced long-term (24 h) 40% reduction in both mRNAs when compared to control tissues. PMA induced a rapid and prolonged increase in c-Fos and c-Jun nuclear localization, which was not attenuated by co-incubation with dexamethasone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of dexamethasone on cytokine and phorbol ester stimulated c-Fos and c-Jun DNA binding and gene expression in human lung. 771 92


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