UNIPROT:P05412 - FACTA Search

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

The pattern of expression of fos and jun family immediate early genes following the induction of long-term potentiation (LTP) was investigated in the dentate gyrus of awake rats. Rapid, transient increases in the levels of c-jun and jun-B mRNA and protein, and in the levels of Fos-related proteins (FRAs), occurred in the dentate gyrus after LTP-inducing tetanization of the perforant path. A delayed, and more prolonged induction occurred for jun-D mRNA and protein. The induction of c-Jun, Jun-B, Jun-D and Fos-related proteins was prevented by administration of an N-methyl-D-aspartate receptor antagonist, which also blocked LTP induction, and by pentobarbital, which reduced but did not block LTP. These findings show that differential expression of fos and jun gene family members occurs in a distinct pattern following LTP in awake rats. The responsive genes may participate in the biochemical cascade leading to the long-term stabilization of synaptic modifications.
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PMID:Differential expression of immediate early genes after hippocampal long-term potentiation in awake rats. 851 May

The response of the kidney to ischemic injury includes increased DNA synthesis, which is preceded by rapid and brief expression of the c-fos proto-oncogene. While the timing of these two events would suggest that c-Fos participates in an immediate-early gene program leading to proliferation, no direct test of this hypothesis exists. The purpose of these studies was (1) to determine whether c-fos is expressed as part of a typical immediate-early (IE) gene response, which would require co-expression of c-jun and sensitivity to cycloheximide, and (2) to determine whether the cells expressing c-Fos are the same as those undergoing DNA synthesis. Northern analysis was performed on renal mRNA at different times following release of a 50 minute period of renal hilar clamping. c-jun and c-fos mRNA were rapidly and briefly expressed following renal ischemia and their expression was superinduced by cycloheximide in a manner typical of an immediate-early gene response. 3H-thymidine autoradiography performed on semi-thin sections from intravascularly perfusion fixed kidneys 24 hours following induction of ischemia showed labeled nuclei in cells lining the damaged proximal tubules of the outer stripe of the outer medulla, as well as proximal tubules in the cortex and interstitial cells throughout the kidney. However, immunohistochemical localization of c-Fos and c-Jun protein occurred predominantly in nuclei of the thick ascending limb, distal tubule and collecting duct cells. The studies demonstrate that c-fos and c-jun are expressed following renal ischemia as a typical immediate-early gene response, but they are expressed in cells that do not enter the cell cycle. The failure of the cells to enter the cell cycle may depend on the co-expression of jun-B and jun-D, which suppress the mitogenic activity of c-Jun in other cells. The data suggest that the IE response following renal ischemia is part of the stress response, which is antiproliferative rather than proliferative. The role of the stress response during renal ischemia and the fate of the cells undergoing it are unknown.
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PMID:DNA synthesis is dissociated from the immediate-early gene response in the post-ischemic kidney. 854 1

Activator protein 1 (AP1) family proteins have been implicated in the regulation of genes expressed in the epidermis. However, no comprehensive analysis of the expression patterns of the known AP1 family proteins in the human epidermis or any other terminally differentiating tissue has been performed. In the present study we describe the localization of c-fos, fosB, Fra-1, Fra-2, c-jun, junB and junD in the normal human epidermis. Each is expressed in specific epidermal layers. c-fos is localized in the nuclei of the upper spinous and granular layer cells. FosB is present in the nuclei in all layers. Fra-1 is absent from the basal layer, but is present in all other layers. Fra-2 is detected in all layers, but staining intensity is increased in the upper spinous layer. c-jun staining is limited to the granular layer, while junB and junD are present in all layers. The differentiation-dependent pattern of expression of the AP1 family members suggest an important role for these proteins in specifying the temporal and spatial pattern of gene expression during keratinocyte differentiation.
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PMID:Differential expression of the fos and jun family members c-fos, fosB, Fra-1, Fra-2, c-jun, junB and junD during human epidermal keratinocyte differentiation. 854 26

Immunocytochemistry was used to localize members of the Jun family of immediate-early genes in the forebrain and midbrain of non-stimulated male rats. Antibodies against specific peptide sequences of c-Jun (Ab-1 and Ab-2 from Oncogene Science) and against expressed proteins of JunB and JunD (both from Dr. R. Bravo) revealed widespread and unique distributions for each of these antigens. Charts were made of the distribution of each antigen, and extensive comparisons were made of previous results obtained using in situ hybridization to localize mRNAs for c-jun, junB and junD. Our results indicate a generally favorable comparison between immunoreactivity and distribution of mRNAs for JunB and JunD, but in the case of c-Jun, immunoreactivity and mRNA were comparable only with the Ab-1 antibody. Indeed, the immunocytochemical distribution of the antigen recognized by the c-Jun Ab-2 antibody was distinctly different from that of the other Jun proteins or mRNAs in the rat brain. This antibody (Ab-2) recognized a nuclear protein found extensively in the caudate-putamen, nucleus accumbens, layer II of the olfactory tubercle, the central nucleus of the amygdala, and the lateral division of the bed nucleus of the stria terminalis. Scattered labeled nuclei were found in a few other forebrain structures. Within the caudate-putamen, immunoreactivity was restricted to the matrix compartment, as determined by immunostaining of adjacent sections with the matrix-marker calbindin D28k. Western blots of caudate-putamen demonstrated that this antibody recognized a protein doublet of molecular masses approximately 37 and 34 kDa, distinct from the molecular masses of c-Jun, JunB and JunD. This unique neuroanatomical distribution and molecular mass suggests that this antibody recognizes a previously undescribed Jun-related antigen.
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PMID:Charting of Jun family member proteins in the rat forebrain and midbrain: immunocytochemical evidence for a new Jun-related antigen. 854 92

The present study was designed to compare the expression of the Jun family of protooncogenes following nerve injury. Adult rats were anesthetized and the sciatic nerve transected. Dorsal root ganglia (DRG) at 1, 2, 3, and 7 days after nerve transection were collected, their total RNA extracted, and Northern blots performed using 32P-labeled oligonucleotide probes. The constitutive expression of c-jun mRNA was very low in DRG. Induction of c-jun mRNA was observed by day 1 after nerve transection, with a sixfold peak at 3 days and a twofold induction still present by day 7. The constitutive expression of junB mRNA was also low in the DRG, and sciatic nerve transection produced only a modest induction (1.7-fold by day 3) in the DRG ipsilateral to the nerve cut. junD mRNA was constitutively expressed at high levels in the DRG, and its level of expression did not in the DRG, and its level of expression did not change after sciatic nerve transection. Immunocytochemistry studies demonstrated a pattern of c-Jun, JunB, and JunD immunoreactivity (IR) associated with the cell nuclei of DRG neurons. c-Jun IR was found at very low levels in the undamaged contralateral DRG neurons, but sciatic nerve transection dramatically increased the number of c-Jun-immunoreactive neurons. Dot blot immunoblotting assay confirmed that the DRG ipsilateral to the sciatic nerve cut contained a higher level of c-Jun protein than the contralateral control DRG. Similar to c-Jun IR, JunB IR was minimal in the undamaged contralateral DRG. However, the DRG ipsilateral to the nerve transection did not show an increase in the number of immunoreactive neurons. JunD protein was expressed at high levels in the contralateral DRG, and this level of expression persisted after sciatic nerve transection in the ipsilateral DRG. DNA gel retardation assay experiments with an AP-1 consensus sequence showed a single DNA-protein complex. This complex was increased in ipsilateral as compared with contralateral DRG extracts. The amount of DNA-protein complex was reduced by c-Jun protein antiserum but was not altered when treated with a Fos antibody. We conclude that c-jun, junB and junD mRNAs and proteins are differentially regulated in the DRG after sciatic nerve transection.
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PMID:Comparison of c-jun, junB, and junD mRNA expression and protein in the rat dorsal root ganglia following sciatic nerve transection. 858 8

The jun genes (c-jun, jun-B and jun-D) play a role in critical cell functions such as proliferation, differentiation and apoptosis. We documented jun expression at the mRNA and protein level in human ovarian cancer tissues (n=28), surface epithelial cells of normal ovaries (n=14) and ovarian cancer cell lines (n=6). Almost all of ovarian tumors as well as normal ovaries concomitantly express c-jun, jun-B, and jun-D mRNA. Immunohistochemistry was less sensitive and revealed nuclear c-Jun and Jun-B proteins in the malignant epithelial cells of respectively 38% and 11% of ovarian tumors and in the surface epithelium of a normal premenopausal ovary. In cultured ovarian cancer cells, c-jun and jun-B expression is inducible by serum and TPA and is therefore not constitutive. The c-jun and jun-B proteins therefore play a role both in differentiation of the normal ovarian surface epithelium, as well as in the proliferation of epithelial ovarian cancer cells. High jun-B expression relates to a more malignant phenotype both in vitro and in vivo. The jun-D gene is suppressed in ovarian cancer cells as compared to normal ovarian surface epithelial cells in situ and in vitro. Downregulation of jun-D might therefore be part of the malignant ovarian epithelial cell phenotype.
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PMID:Expression of the jun family of genes in human ovarian cancer and normal ovarian surface epithelium. 864 27

In Syrian hamster liver, treatment with 3-methylcholanthrene (3-MC) markedly induces an isozyme of cytochrome P450 (CYP), CYP2A8. To elucidate the mechanism of this induction, we studied the effect of okadaic acid (OA), an inhibitor of serine threonine protein phosphatases 1 and 2A, on 3-MC-induced CYP2A8 expression in primary cultures of Syrian hamster hepatocytes. The addition of OA to the cultured hepatocytes at a concentration of 1 nM potentiated 3-MC- (0.1 and 1 microM) induced expression of mRNA and protein of CYP2A8 and its associated coumarin 7-hydroxylase activity. In addition, OA not only induced c-fos and jun-D mRNA, components of transcription factor activator protein-1 (AP-1), with an increase in AP-1 binding activity in the nucleus, but also activated AP-1-dependent gene transcription in the hepatocytes. The dose-dependent effect of OA on 3-MC-induced CYP2A8 expression corresponded to that of OA on c-fos and jun-D mRNA induction and on the activation of AP-1-dependent gene transcription. The expression of c-fos and jun-D mRNA induced by OA preceded the expression of CYP2A8 mRNA potentiated by co-treatment with 3-MC and OA. Treatment with anisomycin and cycloheximide also potentiated 0.1 microM 3-MC-induced coumarin 7-hydroxylase activity, induced c-fos and jun-D mRNA expression, and activated AP-1-dependent gene transcription in the hepatocytes. Furthermore, 3-MC-induced CYP2A8 expression was potentiated in the hepatocytes transfected with c-Jun expression plasmid. These results suggest that AP-1, inducible by serine threonine protein kinase, may be one of the components of the signal transduction system from 3-MC to CYP2A8 gene expression.
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PMID:Okadaic acid potentiates 3-methylcholanthrene-induced CYP2A8 gene expression in primary cultures of Syrian hamster hepatocytes: possible involvement of activator protein-1. 879 94

Halogenated aromatic hydrocarbons, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin), and polycyclic aromatic hydrocarbons, such as benzo[a]pyrene, are environmental contaminants that cause many apparently unrelated toxic effects. In a previous study, we have shown that treatment of mouse hepatoma cells with TCDD or B(a)P results in an increase in mRNA levels of the immediate-early protooncogenes c-fos, c-jun, junB, and junD, and the concomitant increase of the DNA-binding activity of the transcription factor AP-1, a dimer of FOS and JUN proteins. To analyze the mechanism of fos/jun activation by TCDD we have used electrophoretic mobility shift and transient expression assays of reporter gene constructs containing response elements for 12-O-tetradecanoyl-phorbol-13-acetate (TRE), serum (SRE), cAMP (CRE), and aromatic hydrocarbons (AhRE) from the fos and jun genes fused to the firefly luciferase gene under the control of the SV40 minimal promoter. In mouse hepatoma Hepa-1 cells, which have Ah receptor (AHR) and Ah receptor nuclear translocator (ARNT) proteins, inclusion of TRE, SRE, and the AhRE motifs from c-jun and junD, but not CRE or the AhREs from c-fos, fosB, and junB, causes a large TCDD-dependent increase in luciferase expression. In agreement with these results, c-jun and junD, but not c-fos, fosB, and junB AhREs, competed with a canonical Cyp1A1 AhRE for binding to the AHR ARNT heterodimeric complex. In African Green Monkey CV-1 cells, which lack AHR, expression plasmids with AhRE motifs require coexpression of AHR and ARNT for TCDD to stimulate luciferase expression. In contrast, SRE-containing expression plasmids respond equally well to TCDD whether or not AHR and ARNT are coexpressed. These results suggest that TCDD induces expression of the immediate-early response genes fos and jun by activation of possibly three separate signal transduction pathways, at least one of which does not require a functional Ah receptor complex.
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PMID:Dioxin induces transcription of fos and jun genes by Ah receptor-dependent and -independent pathways. 891 96

Differentiation of 3T3T cells into adipocytes results in the progressive repression of growth factor responsiveness. This is associated with the transcriptional repression of the inducibility of c-jun and junB expression by serum. In contrast, differentiation of SV-40 large T antigen-transformed 3T3T cells (CSV3-1) does not repress growth factor responsiveness nor c-jun or junB inducibility even though CSV3-1 cells can differentiate into adipocytes. To better explain these observations, we have studied compositional changes in AP-1 DNA binding activity attributed to c-Jun, JunB, and JunD during the differentiation process in 3T3T and CSV3-1 cells. The results show that in nontransformed 3T3T cells, differentiation represses AP-1 DNA binding activity via a proportionate downregulation of c-Jun, JunB, and JunD. In contrast, in CSV3-1 cells, AP-1 DNA binding activity increases twofold during differentiation, which is accounted for by an increase in JunD with no change in c-Jun and JunB. If c-Jun and JunB serve as positive regulators and JunD serves as a negative regulator for cell proliferation as suggested by previous studies, the repression of JunD expression in differentiating CSV3-1 cells should be mitogenic because decreasing JunD/AP-1 DNA binding activity would allow c-Jun/AP-1 and JunB/AP-1 DNA binding activities to be dominant. The results confirm this prediction showing that antisense junD oligodeoxyribonucleotides are mitogenic for differentiating CSV3-1 cells whereas antisense c-jun and junB inhibit mitogenesis. These data support the conclusion that differentiation can regulate cellular proliferative potential by modulating the balance of positive and negative Jun/AP-1 DNA binding activities in distinct ways in nontransformed and transformed cells.
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PMID:Differentiation modulates the balance of positive and negative Jun/AP-1 DNA binding activities to regulate cellular proliferative potential: different effects in nontransformed and transformed cells. 892 93

An early and immediate response of cells upon irradiation with UV light and various other forms of genotoxic stress is the induction of the proto-oncogenes c-fos and c-jun. To address the questions of whether (a) methylating agents that are powerful carcinogens are effective in induction of fos and jun mRNAs, (b) induction is affected by the repair capacity of the cells, and (c) induction is accompanied by genotoxic effects, the levels of c-fos, c-jun, junB and junD mRNA were analysed in isogenic Chinese hamster cell lines deficient (phenotypically Mex-) and proficient (Mex+) for the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) after treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and methyl methanesulfonate (MMS). Both methylating agents were very effective in inducing fos and jun mRNAs, although they differ markedly in their potency to induce O6-methylguanine in DNA. Most responsive were c-fos and c-jun (up to 80-fold increases in mRNA level) whereas junB (up to ninefold) and junD (up to twofold) displayed an intermediate and weak response, respectively. No difference in the dose-dependence of induction of these mRNAs was observed between Mex- and Mex+ cells indicating that the critical genotoxic and mutagenic lesion induced by MNNG, i.e. O6-methylguanine, which is rapidly repaired by MGMT, does not act as a trigger for this response. Induction of fos and jun mRNAs by MNNG and MMS was accompanied by a dose-dependent increase in the activity of the transcription factor AP-1. To induce fos and jun mRNAs as well as AP-1, doses of MNNG were required which were more than 50-fold higher than those inducing gene mutations, recombination events (SCEs) and reproductive cell death, and fivefold higher than those inducing chromosomal aberrations in Mex cells. Therefore, the immediate induction of fos and jun mRNAs and AP-1 in Mex- cells upon their exposure to MNNG appears not to be essential for the generation of MNNG-induced mutagenic and genotoxic effects, which is possibly due to the high genotoxic potential of non-repaired O6-methylguanine. However, for MMS and UV light, which was included in this study for comparison, c-fos, c-jun, junB and junD mRNA as well as AP-1 induction paralleled the dose-response for induction of cell killing effects, recombination and chromosomal breakage indicating that increased expression of Fos and Jun is related to the generation of MMS and UV-induced genetic changes. These data are in line with a model according to which the induced c-Fos and Jun proteins are involved in defense against UV radiation and other DNA damaging agents.
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PMID:Induction of c-fos, c-jun, junB and junD mRNA and AP-1 by alkylating mutagens in cells deficient and proficient for the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) and its relationship to cell death, mutation induction and chromosomal instability. 893 39

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