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

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

A newly recognized class of eukaryotic transcription factors is characterized by a bipartite sequence motif, consisting of a C-terminal dimerization region (the leucine zipper) and an N-terminal basic region (which mediates DNA binding). In studies of isolated leucine zipper peptides, the dimerization region has been characterized as a coiled coil of parallel alpha-helices. To extend these studies to a functional DNA-binding domain, we describe CD studies of the thermal unfolding and refolding of a 58-residue fragment of GCN4, the yeast homologue of the c-Jun protooncoprotein. This fragment, which contains the complete leucine zipper and basic region, retains the DNA-binding properties of the intact protein. The GCN4 DNA-binding domain exhibits two independent helix-coil unfolding transitions. The major transition (midpoint 65 degrees C) is due to dissociation of the dimer in accord with previous studies of an isolated leucine zipper. A novel pretransition in the temperature range 0-40 degrees C is also observed, which reflects partial stabilization of the nascent helix in the basic region. Remarkably, complete folding of the basic region as an alpha-helix requires specific DNA binding, and the protein-DNA complex exhibits a single cooperative unfolding transition. These results support a major feature of the recently proposed "scissor's grip" model of DNA recognition, in which the basic regions extend from the leucine zipper as bifurcating alpha-helical arms.
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PMID:Thermal unfolding studies of a leucine zipper domain and its specific DNA complex: implications for scissor's grip recognition. 226 59

The cyclic AMP response element (CRE) is found in many cellular genes regulated by cyclic AMP, and similar elements are present in the early genes of adenovirus that are activated by E1A. The transcription factor CREB has previously been shown to bind this site, and cDNAs for CREB have recently been characterized. We report here the isolation of a cDNA encoding a human DNA-binding protein that also recognizes this motif in cellular and viral promoters. This protein, HB16, displays structural similarity to CREB and to c-Jun and c-Fos, which bind the related 12-O-tetradecanoylphorbol-13-acetate response element (TRE). HB16 contains a highly basic, putative DNA-binding domain and a leucine zipper structure thought to be involved in dimerization. Deletional analysis of HB16 demonstrated that the leucine zipper is required for its interaction with DNA. In addition, HB16 could form a complex with c-Jun but not with c-Fos. Despite its structural similarity to c-Jun and c-Fos and its interaction with c-Jun, HB16 had approximately a 10-fold-lower affinity for the TRE sequence than for the CRE sequence. Although HB16 and CREB both recognized the CRE motif, an extensive binding analysis of HB16 revealed differences in the fine specificity of binding of the two proteins. HB16 mRNA was found at various levels in many human tissues but was most abundant in brain, where its expression was widespread. The existence of more than one CRE-binding protein suggests that the CRE motif could serve multiple regulatory functions.
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PMID:A cDNA for a human cyclic AMP response element-binding protein which is distinct from CREB and expressed preferentially in brain. 232 2

The protooncogene c-jun encodes a component of the transcription factor AP-1. Both murine c-jun and a related gene (jun-B) are rapidly activated in BALB/c3T3 cells by serum growth factors. We report here the cloning and analysis of a cDNA encoding a third member of the murine jun family, jun-D. The amino acid sequence encoded by jun-D has two extensive regions of homology with the other Jun proteins. One homology region includes the DNA-binding domain and sequences required for dimer formation and interaction with the Fos oncoprotein; the other includes the acidic sequence thought to be involved in gene activation. All three jun mRNAs are present in a variety of murine tissues and cell lines. In resting 3T3 cells, jun-D is expressed at a higher level compared to c-jun and jun-B, and its transcription is stimulated only slightly by serum growth factors. Thus, jun-D appears to be regulated differently than c-jun and jun-B.
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PMID:jun-D: a third member of the jun gene family. 249 44

The adenovirus early region 3 (E3) promoter is an early viral promoter which is strongly induced by the adenovirus transactivator protein E1A. DNase I footprinting with HeLa cell extracts has identified four factor-binding domains which appear to be involved in basal and E1A-induced transcriptional regulation. These binding domains may bind TATA region-binding factors (site I), the CREB/ATF protein (site II), the AP-1 protein (site III), and nuclear factor I/CTF (site IV). Recently, it has been shown that the DNA-binding domain of transcription factor AP-1 has homology with the yeast transcription factor GCN4 and that the yeast transactivator protein GAL4 is able to stimulate transcription in HeLa cells from promoters containing GAL4-binding sites. These results suggest an evolutionary conservation of both transcription factors and the mechanisms responsible for transcriptional activation in Saccharomyces cerevisiae and higher eucaryotic organisms. To determine whether similar patterns of transcriptional regulation were seen with the E3 promoter in HeLa and yeast cells, the E3 promoter fused to the chloramphenicol acetyltransferase (cat) gene was cloned into a high-copy-number plasmid and stably introduced into yeast cells. S1 analysis revealed that similar E3 promoter mRNA start sites were found in yeast and HeLa cells. DNase I footprinting with partially purified yeast extracts revealed that four regions of the E3 promoter were protected. Several of these regions were similar to binding sites determined by using HeLa cell extracts. Oligonucleotide mutagenesis of these binding domains indicated their importance in the transcriptional regulation of the E3 promoter in yeast cells. These results suggest that similar cellular transcription factor-binding sites may be involved in the regulation of promoters in both yeast and mammalian cells.
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PMID:Adenovirus transcriptional regulatory regions are conserved in mammalian cells and Saccharomyces cerevisiae. 297 53

Androgen receptor (AR) brings about a ligand-dependent inhibition of low-affinity neurotrophin receptor (p75) promoter constructs in cultured cells, with the greatest inhibition being achieved with a reporter gene containing 1050 nucleotides (nt) of the promoter. The receptor domain critical for trans-repression localizes to the same region (amino acids 147-296) as that mandatory for transactivation. In contrast to trans-activation, AR does not interact directly with specific DNA elements to elicit trans-repression of p75 promoter constructs, although an intact DNA-binding domain of the receptor is required for both actions. In a search for interacting partners, both extensively purified full-length AR and AR-DNA binding domain were found to inhibit c-Jun/AP-1 site interaction without themselves binding to the AP-1 element. Prior binding of c-Jun to the AP-1 element protected the complex from the receptor's interference. Repression was not mutual, as c-Jun did not inhibit AR-androgen response element interaction or trans-activation through an androgen response element-containing promoter. The 1050-nt-long p75 promoter sequence does not contain an AP-1 element; an AP-1-like site in the vector backbone mediates the trans-repression by the AR in recipient cells. Intriguingly, an AR form with a large N-terminal deletion (the delta 46-408 mutant) behaved as a transcriptional activator of the p75 promoter through a mechanism that was also independent of specific DNA binding. Collectively, these data indicate that, in a proper context, AR is able to elicit both transrepression and trans-activation without interacting directly with specific DNA elements. Sequences responsible for the down-regulation of p75 mRNA by androgens in vivo are, however, not located in the proximal 1050 nt of the p75 promoter.
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PMID:Androgen receptor-mediated transcriptional regulation in the absence of direct interaction with a specific DNA element. 747 76

The DNA binding activity of transcription factor AP-1 is regulated in vitro by a posttranslational mechanism involving reduction/oxidation (redox). Redox regulation is mediated by a conserved cysteine residue in the DNA-binding domain of Fos and Jun. Previously, we demonstrated that a DNA repair protein, Ref-1, could stimulate the DNA binding activity of Fos-Jun dimers by reducing this cysteine residue. To examine the relationship between the redox and repair functions of Ref-1, we generated a series of deletion mutants. Analysis of the truncated proteins in vitro revealed that the redox and repair activities are encoded by distinct regions of Ref-1. Sequences in the N-terminal domain of Ref-1 that are not present in functionally related proteins from other organisms are required for the redox activity, whereas the DNA repair activity requires conserved C-terminal sequences. Chemical alkylation or oxidation of cysteine sulfhydryls inhibits the redox activity of Ref-1 without affecting its DNA repair activity. Crosslinking studies suggest that a direct cysteine-mediated interaction occurs between Ref-1 and Jun.
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PMID:The redox and DNA-repair activities of Ref-1 are encoded by nonoverlapping domains. 750 14

A human cDNA clone for ERM, a member of the ets gene family, has been obtained by polymerase chain reaction with degenerate primers corresponding to highly conserved regions within an Ets DNA binding domain. ERM mRNA is expressed ubiquitously. The gene was mapped to chromosome 3q27. In in vivo transient-expression assays, ERM induced transcription more efficiently from a synthetic element containing both an ets-binding site (EBS) and a cyclic AMP response element (CRE) than from one containing an EBS alone. The activation of a synthetic EBS-CRE site by ERM was likely to involve a leucine zipper protein capable of dimerizing with CRE-BP1 leucine zipper. Indeed, ERM and c-Jun synergistically activated the EBS-CRE without making an apparent ternary complex. The synergy between c-Jun and ERM may be attributed to the enhancing effect of c-Jun on the transcription activity of ERM, because c-Jun increased ERM transcription activity by more than 20-fold in an assay system using a variety of fusion proteins between a Gal4 DNA-binding domain and a portion of ERM. This enhancing effect of c-Jun required the amino-terminal portion of ERM.
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PMID:ERM, a PEA3 subfamily of Ets transcription factors, can cooperate with c-Jun. 755 55

We have examined the 5'-flanking region (944 bp) of the human choline acetyltransferase (hChAT) gene for sequences that modulate its transcriptional activity and identified a sequence 5'-TGACCCA-3' which confers c-Jun/c-Fos (AP-1) inducibility of homologous and heterologous promoters. Using transient transfections in neuroblastoma NE-1-115 and COS-1 cells, we show that ligand-activated estrogen receptor (HEGo) represses the transcriptional activation by c-Fos/c-Jun. Testing HEGo mutants in transfection assays reveals that the ligand-binding domain is crucial for this repression, whereas the N-terminal (A/B) region and the DNA-binding domain are not essential. Gel retardation assays show that the hChAT AP-1 recognition sequence binds in vitro baculovirus-produced c-Jun/c-Fos proteins. This binding is inhibited by addition of baculovirus-produced HEGo. In contrast to HEGo, ligand-activated glucocorticoid, androgen, and retinoic acid receptors (RARs) enhance the transcription activation induced by c-Jun/c-Fos. All three types of RARs--RAR alpha, beta, gamma--and RXR alpha are able to stimulate AP-1 activity on the proximal hChAT promoter. Several mechanism possibilities involving protein-protein interaction are discussed to explain the phenomena.
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PMID:Positive and negative effects of nuclear receptors on transcription activation by AP-1 of the human choline acetyltransferase proximal promoter. 774 8

Marek's disease virus (MDV) is an avian herpesvirus that induces a variety of diseases, including T-cell lymphomas, in chickens. In latently infected, transformed lymphoid cells, very few viral transcripts or proteins are detected. We previously described a gene, meq (MDV EcoQ), which is persistently expressed in MDV-transformed tumor samples and cell lines. meq codes for a 339-amino-acid protein with a basic-leucine zipper domain near its N terminus and a proline-rich domain near its C terminus. The basic-leucine zipper domain shows homology with Jun/Fos family proteins, whereas the proline-rich domain resembles that of the WT-1 tumor suppressor protein. These structural features raise the possibility that Meq functions as a transcription factor in regulating viral latency or oncogenesis. In this report, we show that the proline-rich domain is a potent transcription activator when fused to the yeast (Saccharomyces cerevisiae) Gal4(1-147) DNA-binding domain. The transactivation activity maps to the C-terminal 130 amino acids, with the last 33 amino acids essential. In the absence of these 33 amino acids, a two-and-one-half proline-rich repeat structure was found to exhibit repression activity. We further show that Meq is able to dimerize not only with itself but also with c-Jun. Meq/c-Jun heterodimers bind to an AP1-like sequence in the meq promoter region with an affinity much greater than that of Meq/Meq or c-Jun/c-Jun homodimers. Cotransfection chloramphenicol acetyltransferase assays suggest that the Meq/c-Jun heterodimers can up-regulate Meq expression in both chicken embryo fibroblasts and F9 cells. Our data provide the first biochemical evidence that Meq is a transcriptional factor and identify c-Jun as one of Meq's interacting partners.
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PMID:Transactivation activity of Meq, a Marek's disease herpesvirus bZIP protein persistently expressed in latently infected transformed T cells. 776 61


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