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

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

We have studied interactions between bacterially produced E1A linked to Sepharose and the various DNA-binding proteins present in HeLa cell nuclear extracts (NE). DNA-binding activities and cross-reactive polypeptides recognizing the cAMP-responsive element (CRE) and the activator protein 1 (AP1) sites were bound to the E1A column, whereas nuclear factor 1 (NF1) and the activator protein 2 (AP2) DNA-binding activities were not retained by E1A. The binding activities that were retained belonged to the CRE and JUN protein family, as judged by Western blot analysis. Authentic CRE-BP1, c-Jun and c-Fos proteins produced by in-vitro translation also bound to the E1A column. However, efficient binding of in-vitro-translated CRE-BP1 and c-Fos proteins to E1A required preincubation with NE. We show here that immobilized E1A sequesters several cellular upstream transcription activators, and suggest a role for members of the AP1 family of transcription factors in E1A-mediated gene regulation.
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PMID:Interactions between adenovirus E1A and members of the AP-1 family of cellular transcription factors. 183 15

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

The response of a cell to mitogens and differentiation agents involves the transcriptional induction of several cellular genes. Prominent among these so-called 'immediate early' or 'competence' genes are the nuclear oncogenes fos and myc. Although the precise function of these early response genes in growth control is not understood, it is likely that many of them are involved in the transition from G0 to G1 in the cell cycle. The findings that the products of nuclear proto-oncogenes jun and erbA are transcriptional factors supports the notion of the role of the nuclear oncoproteins in the regulation of gene expression. Recently, it has been reported that the FOS protein is associated in transcriptional complexes with the product of the jun oncogene, the transcription factor AP-1. As the fos gene is induced in response to mitogens during initiation of cell growth, we investigated whether expression of the nuclear transcription factor AP-1 is also inducible. We report that mouse c-jun gene transcription is rapidly induced by serum and phorbol-ester 12-o-tetradecanoyl phorbol 13-acetate (TPA). Furthermore, induction is transient and the mRNA is superinduced by inhibitors of protein synthesis.
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PMID:Induction of proto-oncogene JUN/AP-1 by serum and TPA. 245 72

The jun oncogene of ASV17 is expressed as a 65 kd protein (p65gag-jun) that contains partial gag sequences at its amino terminus fused to jun sequences that make up the carboxy terminal two-thirds of the molecule. As a first step toward evaluating potential functional differences between the activated oncogene, v-jun, and its cellular counterpart, c-jun, we have characterized the biochemical properties of the gag-jun product of ASV17. Immunofluorescence studies revealed that the v-jun protein is localized in the nucleus of CEF transfected with ASV17 DNA. DNAase I foot-printing analysis indicates that p65gag-jun synthesized in bacteria binds to enhancer elements in SV40 that are recognition sites for the human transcription factor AP-1. Analysis of point mutants confirmed that v-jun protein binds with DNA sequence specificity of the mammalian enhancer factor AP-1 and the yeast transcription factor GCN4. These findings suggest that activation of the jun oncogene may not exclusively be the result of alterations in the DNA binding properties of the normal cellular protein.
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PMID:v-jun encodes a nuclear protein with enhancer binding properties of AP-1. 283 Sep 89

The oncogene jun is the putative transforming gene of avian sarcoma virus 17; jun appears to be derived from a gene of the chicken genome and has homologues in several other vertebrate species. Recent genetic and immunological data indicate that jun codes for a protein that is closely related and probably identical to the transcription factor AP-1. We have isolated a genomic DNA clone encompassing the human cellular counterpart of the gene, JUN, and used this DNA to determine the chromosomal location of the gene. A panel of DNA preparations derived from rodent-human somatic cell hybrids with defined chromosome complements was first screened with the JUN probe. This Southern blot analysis indicated that JUN is situated on the short arm of chromosome 1. In situ hybridization then assigned JUN to chromosome region 1p31-32, a chromosomal region involved in both translocations and deletions of chromosomes seen in human malignancies.
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PMID:Localization of the human JUN protooncogene to chromosome region 1p31-32. 312 28

The JUN protooncogene encodes a protein that is functionally and biochemically identical to the transcription factor AP-1 (activator protein 1). To understand the structure and regulation of this important gene, a genomic clone of human JUN was isolated and its primary structure and transcription pattern were determined. Most surprisingly, the sequence of the genomic clone was found to be contiguous with the sequence of the JUN cDNA, suggesting that it lacks introns. RNase protection experiments confirm that JUN is an intronless gene that yields several transcripts due to 5' and 3' heterogeneities. Transfection experiments show that the cloned gene is functional, as it encodes a trans-acting factor that stimulates transcription of AP-1-dependent reporter gene. In situ hybridization was used to map JUN to chromosomal region 1p31-32. Interestingly, this region is frequently deleted in neuroblastomas, suggesting that elimination of AP-1 may play an important role in the pathogenesis of this disease.
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PMID:Structure and chromosomal localization of the functional intronless human JUN protooncogene. 319 15

The P-450 side chain cleavage (CYP11A1) gene encodes the enzyme that catalyzes the initial step in steroid biosynthesis, resulting in the conversion of cholesterol to pregnenolone. Expression of the CYP11A1 gene is increased by hormones, such as adrenocorticotropin and luteinizing hormone, as well as by a number of growth factors, suggesting that its promoter may contain regulatory elements that respond to multiple signal transduction pathways. Using transient expression assays of the ovine CYP11A1 promoter in JEG-3 placental cells, distinct regulatory elements were found to mediate transcriptional stimulation by cAMP and epidermal growth factor (EGF). The cAMP response was mediated through a GC-rich sequence localized between -117 and -92. In contrast, EGF induced CYP11A1 transcription through an adjacent but distinct sequence (-92 to -77 base pairs) that was shown previously to bind nuclear proteins in DNase I footprinting reactions. This EGF-responsive element (EGF-RE) resembles an activator protein-1 (AP-1) site and was also required for transactivation by co-transfected c-Jun. A point mutation within the EGF-RE impaired stimulation by both EGF and c-Jun, suggesting that these pathways converge on a common regulatory element. Transfer of single or multiple copies of the EGF-RE upstream of an heterologous promotor conferrd EGF and c-Jun responses, providing further evidence that this element is sufficient for both responses. Transfection studies employing mutant c-Jun proteins confirmed a requirement for its DNA binding, leucine zipper and amino-terminal domains, each of which are required for activation of a classical AP-1 reporter. Gel shift studies demonstrated that protein binding to the CYP11A1 EGF-RE was competed specifically by a canonical AP-1 site, and the addition of an anti-JUN antibody confirmed the presence of AP-1 proteins. Consistent with the possibility that EGF may act in part via c-Jun, EGF stimulated the activity of a chimeric GAL4 c-Jun protein, indicating that JUN can serve as a potential target of EGF in JEG-3 cells. EGF also induced mitogen-activated protein kinase activity, and a dominant negative mutant of mitogen-activated protein kinase partially blocked EGF stimulation of GAL4 c-Jun activity. We conclude that EGF stimulates the CYP11A1 promoter through an AP-1 like element and that c-Jun is one of the targets of EGF action.
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PMID:Epidermal growth factor and c-Jun act via a common DNA regulatory element to stimulate transcription of the ovine P-450 cholesterol side chain cleavage (CYP11A1) promoter. 762 50

delta-9-Tetrahydrocannabinol (THC) is a major psychoactive component of cannabis. We have recently localized a receptor for THC in the forebrain and found in the caudate-putamen that its gene expression is modulated by glucocorticoids, dopamine and glutamate. Here, we report for the first time, using quantitative in situ hybridization, that acute THC (5 mg kg-1, i.p.) regulates the mRNA levels of multiple immediate early genes in the adult rat forebrain. Twenty minutes after a single THC injection, significant increases in concentration of the mRNAs for C-FOS, C-JUN and ZIF-268 were observed in the cingulate cortex (75, 45 and 37%) and for C-FOS and ZIF-268 in the fronto-parietal cortex (60 and 64%) and caudate-putamen (81 and 32%) while JUN-D mRNA levels were not changed. These transcription factor genes might mediate putative THC modulation of neurotransmitter gene expression.
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PMID:Activation of multiple transcription factor genes by tetrahydrocannabinol in rat forebrain. 791 80

Chorionic gonadotropin (CG) is a heterodimeric placental hormone encoded by separate alpha and beta subunit genes that is essential for the maintenance of pregnancy. The production of CG is stimulated by DNA synthesis inhibitors and by cAMP. The present study demonstrates that the proto-oncogene c-jun represses transcription of the human CG alpha and CG beta promoters. c-Jun repressed the CG alpha promoter through a canonical cAMP response element (CRE) that is known to bind c-Jun and other members of the B-Zip transcription factor family. In the CG beta promoter, two adjacent sites, CRE1 (-299 to -289) and CRE2 (-240 to -219), conveyed cAMP responsiveness via sequences that are distinct from the canonical element, TGACGTCA. Mutations within CG beta CRE1 or CRE2 reduced or abolished, respectively, c-Jun-mediated repression. Although the CG beta CREs do not contain consensus sequences previously described to bind c-Jun, CRE2 bound c-Jun and c-Fos in electrophoretic mobility shift assays. Supershift assays, using anti-JUN antibody, demonstrated that Jun formed part of the native complex that binds the CRE2 in JEG-3 cells. A series of c-Jun mutants were used to analyze the transcription factor domains required for repression of the CG subunit promoters. The DNA binding and leucine zipper domains of c-Jun as well as the amino terminus, were required for repression of both subunit promoters. Thus, both the CG alpha and CG beta genes are repressed by c-Jun through promoter regions that convey cAMP-induced transcription, although these DNA sequences are unrelated.
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PMID:c-Jun represses transcription of the human chorionic gonadotropin alpha and beta genes through distinct types of CREs. 798 49


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