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

c-Jun/AP-1 is a transcription factor commonly induced in mammalian cells by serum, phorbol compounds, or peptide growth factors. We show that c-Jun/AP-1 is inducible as well as coordinately regulated, in the human acute myelogenous leukemia cell line KG-1, by the cytostatic drug 1-beta-D-arabinofuranosylcytosine (Ara-C). Concomitantly with Ara-C treatment, growth inhibition and loss of clonogenic survival of KG-1 cells were observed. Whereas KG-1 cells displayed only barely detectable amounts of c-jun transcripts when cultured in the presence of serum, Ara-C at concentrations of 1 to 50 microM induced c-jun transcripts in a dose-dependent fashion. Time course studies showed that 10 microM Ara-C induced c-jun transcripts 6 hr after initiation of culture. Induction of c-jun mRNA was independent of de novo protein synthesis, because the protein synthesis inhibitor cycloheximide failed to alter Ara-C-induced c-jun mRNA accumulation. Furthermore, cycloheximide did not induce c-jun transcripts, ruling out the possibility of posttranscriptional stabilization of c-jun mRNA by labile proteins, as has been previously reported for a variety of serum-inducible protooncogenes and early response genes. Moreover, nuclear run-on analysis disclosed that c-jun induction by Ara-C in KG-1 cells took place at a transcriptional level. Taken together, these findings indicate that c-jun mRNA, unlike its rapid (within minutes) induction by serum in fibroblasts, is induced by Ara-C in KG-1 cells following a much more prolonged time course and is regulated essentially at a transcriptional level.
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PMID:Induction of c-jun expression in the myeloid leukemia cell line KG-1 by 1-beta-D-arabinofuranosylcytosine. 1721 95

The mammalian transcription factor AP-2 is a retinoic acid inducible sequence-specific DNA-binding protein that is developmentally regulated. In this report, the functional domains necessary for AP-2 DNA binding were studied. AP-2 required a dimerization domain and an adjacent region of net basic charge to achieve a sequence-specific protein:DNA interaction. The sequences responsible for dimerization consisted of two putative amphipathic alpha helices separated by a large intervening span region. This helix-span-helix (HSH) domain was unable to bind DNA when separated from the basic region, but was still capable of dimerization. The ability of the HSH domain to function as a module that promotes DNA binding through dimerization was further demonstrated by attaching it to the heterologous basic region of the c-Jun proto-oncogene product. The resulting chimeric protein specifically recognized an AP-1 DNA-binding site in the absence of an intact c-Jun leucine repeat and in a manner that was dependent on the presence of a functional AP-2 dimerization domain.
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PMID:Characterization of a dimerization motif in AP-2 and its function in heterologous DNA-binding proteins. 199 22

The human beta-globin locus control region (LCR) is essential for high-level expression of human epsilon-, gamma-, and beta-globin genes. Developmentally stable DNase I hypersensitive sites (designated HS) mark sequences within this region that are important for LCR activity. A 1.9-kilobase (kb) fragment containing the 5' HS 2 site enhances human beta-globin gene expression 100-fold in transgenic mice and also confers position-independent expression. To further define important sequences within this region, deletion mutations of the 1.9-kb fragment were introduced upstream of the human beta-globin gene, and the constructs were tested for activity in transgenic mice. Although enhancer activity was gradually lost with deletions of both 5' and 3' sequences, a 373-base-pair (bp) fragment retained the ability to confer relative position-independent expression. Three prominent DNase I footprints were observed in this region with extracts from the human erythroleukemia cell line K-562, one of which contained duplicated binding sites for transcription factor AP-1 (activator protein 1). When the 1.9-kb fragment containing an 18-bp deletion of the AP-1 binding sites was tested in transgenic mice, enhancer activity decreased 20-fold but position-independent expression was retained.
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PMID:Human beta-globin locus control region: analysis of the 5' DNase I hypersensitive site HS 2 in transgenic mice. 200 Mar 71

The product of the jun proto-oncogene has been identified as one form of the transcription factor AP-1. The p55fos protein associates with jun/AP-1 by means of a heterodimer which requires intact 'leucine zipper' domains of both proteins. The fos/jun heterodimer binds to and activates transcription from TPA-responsive promoter elements (TGACTCA), which represent one final target of the protein kinase C pathway. The other main signal transduction pathway, initiated by the activation of the adenylate cyclase, involves the transcription factor CREB. The promoter element recognized by CREB, a cyclic AMP responsive element (CRE), consist of a palyndromic sequence similar to a TRE (TGACGTCA). We show that jun efficiently trans-activates CRE sequences and that fos and jun efficiently bind and cooperate in activating CRE promoter elements. The similarity between TRE and CRE sequences may involve an interplay in transcriptional regulation and 'cross-talk' between components of the two major signal transduction pathways.
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PMID:Cross-talk in signal transduction: TPA-inducible factor jun/AP-1 activates cAMP-responsive enhancer elements. 210 94

Lesion of the sciatic nerve caused a rapid increase in c-fos and c-jun mRNA that was followed about 2 hr later by an increase in nerve growth factor (NGF) mRNA. To evaluate whether the initial increase in c-fos mRNA is causally related to the subsequent increase in NGF mRNA, we performed experiments with fibroblasts of transgenic mice carrying an exogenous c-fos gene under the control of a metallothionein promoter. In primary cultures of these fibroblasts, CdCl2 evoked a rapid increase in exogenous c-fos mRNA, followed immediately by an increase in endogenous c-jun mRNA and with a slight delay by an increase in NGF mRNA. In fibroblasts of C3H control mice, CdCl2 had no effect on the mRNA levels of the protooncogenes c-fos and c-jun or of NGF. Additional evidence for a causal relationship between c-fos induction and the subsequent increase in NGF mRNA was obtained in cotransfection experiments. Fibroblasts of C3H control mice were cotransfected with a metallothionein-promoter-driven c-fos expression vector and a NGF promoter-chloramphenicol acetyltransferase reporter gene construct. Induction of the exogenous c-fos by CdCl2 resulted in increased activity of the NGF promoter. DNase I footprint experiments demonstrated that a binding site for transcription factor AP-1 (Fos/Jun heterodimer) in the first intron of the NGF gene was protected following c-fos induction. That this protected AP-1 site indeed was functional in the regulation of NGF expression was verified by deletion experiments and by a point mutation in the corresponding AP-1 binding region in the NGF promoter-chloramphenicol acetyltransferase reporter construct.
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PMID:Lesion-induced increase in nerve growth factor mRNA is mediated by c-fos. 211 Oct 20

Transcription factor AP-1 mediates induction of a set of genes in response to the phorbol ester tumor promoter TPA. Recently, AP-1 preparations from HeLa cells were shown to contain a product of the c-JUN protooncogene (Jun/AP-1) which forms a tight complex with the Fos protein. In this paper, we examine the role of the Fos protein in the DNA-binding activity of the AP-1 complex. We show that the DNA-binding activity of bacterially expressed trpE-Jun fusion proteins is increased many-fold upon their interaction with Fos (or a Fos-related antigen) expressed from a baculovirus vector. The site of Fos interaction is within the DNA-binding domain of Jun/AP-1, and anti-Fos antibodies interfere with the binding of affinity purified AP-1 to DNA. These results suggest that, by associating with Jun/AP-1, Fos is responsible for the formation of a multimeric protein complex that has greater affinity for the target sequence than does Jun/AP-1 alone.
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PMID:DNA-binding activity of Jun is increased through its interaction with Fos. 211 28

Cell transformation by oncogenes leads to changes in gene expression. A key event in this process seems to be activation of the transcription factors AP-1 and PEA 3. Their synergistic activities are required for efficient activation of transcription from different promoters by many different oncogenes, serum growth factors and the tumour promoter TPA. We show here that the products of the ets-1 and -2 proto-oncogenes, whose biological function was previously unknown, are transcription factors that activate transcription through the PEA 3 motif. The p68c-ets-1 protein specifically binds to DNA and contains a transcriptional activation domain. The ets-like gene family therefore seems to encode a new family of transcription factors, apparently unrelated to other transcription factors. The p68c-ets-1 protein cooperates with c-Fos and c-Jun (components of AP-1) for activation of transcription from the oncogene-responsive domain of the polyoma enhancer, indicating that combined activity of all three oncoproteins could be involved in the response of cells to growth stimuli.
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PMID:The c-ets proto-oncogenes encode transcription factors that cooperate with c-Fos and c-Jun for transcriptional activation. 211 54

The mechanism by which a single factor evokes opposite regulatory effects from a specific DNA sequence is not well understood. In this study, a 25-base pair element that resides upstream of the mouse proliferin gene was examined; it conferred on linked promoters either positive or negative glucocorticoid regulation, depending upon physiological context. This sequence, denoted a "composite" glucocorticoid response element (GRE), was bound selectively in vitro both by the glucocorticoid receptor and by c-Jun and c-Fos, components of the phorbol ester-activated AP-1 transcription factor. Indeed, c-Jun and c-Fos served as selectors of hormone responsiveness: the composite GRE was inactive in the absence of c-Jun, whereas it conferred a positive glucocorticoid effect in the presence of c-Jun, and a negative glucocorticoid effect in the presence of c-Jun and relatively high levels of c-Fos. The receptor also interacted selectively with c-Jun in vitro. A general model for composite GRE action is proposed that invokes both DNA binding and protein-protein interactions by receptor and nonreceptor factors.
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PMID:Transcription factor interactions: selectors of positive or negative regulation from a single DNA element. 211 54

The BZLF1 or zta immediate-early gene of Epstein-Barr virus (EBV) encodes a 33-kilodalton phosphorylated nuclear protein that is a specific transcriptional activator of the EBV lytic cycle when introduced into latently infected B lymphocytes. We have shown previously that the divergent EBV DSL target promoter contains two zta-response regions, one within the minimal promoter and the other in an upstream lymphocyte-dependent enhancer region. In this study, we used footprinting and gel mobility retardation assays to reveal that bacterially synthesized Zta fusion proteins bound directly to six TGTGCAA-like motifs within DSL. Four of the Zta-binding sites lay adjacent to cellular TATA and CAAT factor-binding sites within the minimal promoter, and two mapped within the enhancer region. Single-copy oligonucleotides containing these Zta-binding sites conferred Zta responsiveness to heterologous promoters. In addition, the Zta protein, which possesses a similar basic domain to the conserved DNA-binding region of the c-Fos, c-Jun, GCN4, and CREB protein family, proved to bind directly to the consensus AP-1 site in the collagenase 12-O-tetradecanoylphorbol-13-acetate response element. Cotransfection with zta also trans activated a target reporter gene containing inserted wild-type 12-O-tetradecanoylphorbol-13-acetate response element oligonucleotides. Cellular AP-1 binding activity proved to be low in latently EBV-infected Raji cells but was induced (together with the Zta protein) after activation of the lytic cycle with 12-O-tetradecanoylphorbol-13-acetate. We conclude that EBV may have captured and modified a cellular gene encoding a c-jun-like DNA-binding protein during its evolutionary divergence from other herpesviruses and that this protein is used to specifically redirect transcriptional activity toward expression of EBV lytic-cycle genes in infected cells.
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PMID:The zta transactivator involved in induction of lytic cycle gene expression in Epstein-Barr virus-infected lymphocytes binds to both AP-1 and ZRE sites in target promoter and enhancer regions. 215 99

Introduction of the zta gene of Epstein-Barr virus into latently infected B cells leads to induction of the entire lytic cycle program of the virus. The Zta gene product is a sequence-specific DNA-binding protein of 35 kilodaltons that behaves as a specific transcriptional transactivator in transient cotransfection assays. All known Zta-responsive target promoters contain one or more members of a family of consensus-binding sites known as ZREs. On the basis of the presence of limited amino acid similarity within a basic carboxy-terminal domain, Zta has been proposed to be a highly divergent member of the c-Jun/c-Fos/GCN4 family of AP-1-binding proteins. We show here that in vitro-translated Zta and the Jun:Fos proteins have overlapping but distinct target DNA-binding specificies; both recognize canonical AP-1 sites, but only Zta recognizes ZRE sites and only Jun:Fos recognizes CRE sites. The relative binding affinity of Zta for oligonucleotides containing the 7-base-pair c-Fos AP-1 site TGAGTCA was twofold greater than that for the ZRE core motifs TGAGCAA, TG TGCAA, and TGAGTAA, but 10-fold greater than that for TGTGTCA, as measured by gel mobility retardation and competition DNA-binding assays. Cross-linking and cotranslational heterodimerization assays showed that like GCN4, Zta forms a stable homodimer in both its DNA-bound and unbound forms. Furthermore, we show that a potential coiled-coil helical domain adjacent to the basic domain of Zta can substitute for the leucine zipper of c-Fos to produce a DNA-binding protein that has a very stringent target DNA specificity and can only recognize symmetric 9-base-pair AP-1 sites (ATGAGTCAT). Therefore, despite the absence of the repeated heptad leucine zipper motifs, the Zta protein retains the characteristic features of a juxtaposed basic region and an exactly aligned coiled-coil alpha-helical dimerization domain of the bZIP class of transcriptional regulatory factors.
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PMID:The Epstein-Barr virus Zta transactivator: a member of the bZIP family with unique DNA-binding specificity and a dimerization domain that lacks the characteristic heptad leucine zipper motif. 216 45


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