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

The proximal region of the ovalbumin gene promoter contains a half-palindromic estrogen-responsive element (ERE) that mediates cell-specific trans-activation by the estrogen receptor (ER). We show that the ovalbumin ERE binds a ubiquitous nucleoprotein complex containing oncoproteins c-Fos and c-Jun. Mutations altering the estrogen inducibility of the promoter prevent the complex formation, which is, however, found in the presence and absence of ER and estradiol. Mutagenesis indicates that the sequence 5'-TGGGTCA-3', containing the half-palindromic ERE, is responsible for induction by phorbol esters of the ovalbumin promoter and is a target for c-fos and c-jun trans-activation. Transfection experiments reveal that c-fos, c-jun, and ER coactivate the ovalbumin promoter. Direct ER interaction with the target sequence is not required, since an ER deleted for its DNA binding domain is functional in the coactivation with c-fos and c-jun. Our data indicate a convergence of hormonal induction and activation of signal transduction pathways at the transcriptional level.
Cell 1990 Dec 21
PMID:Activation of the ovalbumin gene by the estrogen receptor involves the fos-jun complex. 212 18

Interleukin 3 (IL-3 or multi-colony-stimulating factor) plays an important role in the hematopoietic response to inflammatory stimuli through its action on both immature and mature blood cells. Like other lymphokines, IL-3 is produced in response to activation of the T-cell receptor and protein kinase C pathways. By using nuclear run-on assays of quiescent and stimulated T-cell lines, we demonstrate that IL-3 gene expression is controlled, at least in part, at the level of transcription. Functional reporter gene analysis was used to delineate two regions of the IL-3 5' flanking sequence responsible for transcriptional stimulation. DNA binding proteins that potentially mediate these responses were then recognized by mobility-shift and DNase footprinting assays. One region responsible for transcriptional enhancement was localized to the sequence GATGAATAAT, the cognate site of a transcription factor, here termed NF-IL3-A. A second region of functional activity and protein binding was localized to a single transcription factor AP-1 site. In addition three functionally inhibitory regions were identified. These results, along with the further characterization of NF-IL3-A, will contribute to the understanding of IL-3 gene regulation in stimulated T cells.
Proc Natl Acad Sci U S A 1990 Dec
PMID:Transcriptional regulation of interleukin 3 gene expression in T lymphocytes. 226 17

c-Jun, Jun-B, and Jun-D proteins bind to the TPA response element (TRE) either as homodimers or as Jun-Fos heterodimers. We demonstrate that c-Jun and Jun-B nevertheless differ markedly in their ability to activate AP-1 responsive genes. c-Jun is an efficient activator of the c-jun and collagenase promoters, which contain a single TRE; Jun-B is not. Furthermore, Jun-B inhibits activation of these promoters by c-Jun. On the other hand, like c-Jun, Jun-B is an efficient activator of constructs containing multimeric TREs. Using chimeric proteins, we show that the distinct behavior of c-Jun and Jun-B is due to differences in their activation domains. Trans-activation by Jun-B depends on cooperative interactions between adjacently bound factors, while activation by c-Jun does not require such interactions. This differential behavior greatly expands the regulatory potential of the Jun family.
Cell 1989 Dec 22
PMID:Jun-B differs in its biological properties from, and is a negative regulator of, c-Jun. 251 28

Fos protein can trans-activate AP-1-dependent gene expression and trans-repress the c-fos promoter. Although we find that trans-repression is enhanced by coexpression of c-Jun, it does not require any of the AP-1 or ATF sites in the mouse c-fos promoter. A major target for repression is the serum response element (SRE). Fos mutants with an impaired leucine zipper are defective in trans-repression and transformation, suggesting that these functions involve the formation of Fos protein complexes. In contrast, mutations that abolish DNA binding of Fos enhance trans-repression but destroy the transforming potential of Fos. In addition, v-Fos protein efficiently transforms but is unable to trans-repress. These findings point to different mechanisms involved in trans-activation and trans-repression and suggest that trans-repression of the type described here is neither sufficient nor required for Fos-induced transformation.
Cell 1989 Dec 22
PMID:trans-repression of the mouse c-fos promoter: a novel mechanism of Fos-mediated trans-regulation. 251 30

Treatment of adenovirus-infected mouse S49 cells with cAMP analogs leads to the transcriptional induction of early viral genes. E1A proteins and cAMP work in synergy to activate several of these genes. We now demonstrate that the transcription factor AP-1 is modestly induced by cAMP in S49 cells and induced to significantly higher levels by cAMP in the presence of E1A proteins. Cytoplasmic levels of c-fos and junB mRNAs are rapidly increased by cAMP, and the induction is substantially stronger in the presence of E1A protein. The AP-1 activity binds efficiently to both AP-1 and activating transcription factor (ATF)/cAMP response element binding protein (CREB)-binding sites present in E1A-inducible promoters and presumably plays a role in the transcriptional activation of adenovirus genes by E1A proteins and cAMP.
Genes Dev 1989 Dec
PMID:Induction of transcription factor AP-1 by adenovirus E1A protein and cAMP. 255 73

Three members of the Jun/AP-1 family have been identified in mouse cDNA libraries: c-Jun, Jun-B, and Jun-D. We have compared the DNA binding properties of the Jun proteins by using in vitro translation products in gel retardation assays. Each protein was able to bind to the consensus AP-1 site (TGACTCA) and, with lower affinity, to related sequences, including the cyclic AMP response element TGACGTCA. The relative binding to the oligonucleotides tested was similar for the different proteins. The Jun proteins formed homodimers and heterodimers with other members of the family, and they were bound to the AP-1 site as dimers. When Fos translation product was present, DNA binding by Jun increased markedly, and the DNA complex contained Fos. The C-terminal homology region of Jun was sufficient for DNA binding, dimer formation, and interaction with Fos. Our general conclusion is that c-Jun, Jun-B, and Jun-D are similar in their DNA binding properties and in their interaction with Fos. If there are functional differences between them, they are likely to involve other activities of the Jun proteins.
Cell 1988 Dec 02
PMID:DNA binding activities of three murine Jun proteins: stimulation by Fos. 314 91

The c-Jun and c-fos proto-oncogenes encode proteins that form a complex which regulates transcription from promoters containing AP-1 activation elements. c-Jun has specific DNA binding activity, while c-Fos has homology to the putative DNA binding domain of c-Jun. Following in vitro translation, c-Jun binds as a homodimer to the AP-1 DNA site, while c-Fos fails to dimerize and displays no apparent affinity for the AP-1 element. Cotranslated c-Jun and c-Fos proteins bind 25 times more efficiently to the AP-1 DNA site as a heterodimer than does the c-Jun homodimer. These experiments suggest that in growth factor-stimulated cells c-Jun binds DNA as a dimer with c-Fos as its natural partner. However, overexpression of c-Jun protein in the absence of c-Fos may result in formation of aberrant homodimeric transcription complexes, which could abrogate the normal mechanisms controlling gene expression.
Cell 1988 Dec 02
PMID:c-Jun dimerizes with itself and with c-Fos, forming complexes of different DNA binding affinities. 314 92

Gene expression is modulated by the specific interactions of nuclear proteins with unique regulatory sequences in the genome. Proteins involved in transcriptional regulation seem to be either transcription factors or transcription modulators and their interactions are crucial in determining whether the expression of a specific gene is activated or repressed. Recently, the product of the proto-oncogene jun has been identified as the transcription factor AP-1, whereas nuclear oncoproteins fos and myc have been implicated in transcriptional transregulation of several promoters. Furthermore, the products of the fos and jun proto-oncogenes are associated in some transcription complexes. Although the nature of the association is unclear, the two proteins co-immunoprecipitate with fos antibodies in nuclear extracts. Here, we report studies that demonstrate that the fos protein directly modulates jun function by means of a heterodimer of fos and jun proteins. The fos 'leucine zipper' domain is necessary for the DNA binding of the heterodimer; a distinct domain, localized in the C-terminal region of the fos protein, is responsible for transcriptional regulation.
Nature 1988 Dec 15
PMID:Direct interaction between fos and jun nuclear oncoproteins: role of the 'leucine zipper' domain. 314 19

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.
Proc Natl Acad Sci U S A 1988 Dec
PMID:Structure and chromosomal localization of the functional intronless human JUN protooncogene. 319 15

1. The bovine kappa-casein gene has been isolated as a series of overlapping lambda clones and shown to consist of five exons distributed over a total length of approximately 13 kb. Most of the mature protein-coding sequence is contained in a single large exon. 2. Approximately 65% of the gene has been sequenced together with portions of the 5'- and 3'-flanking sequences. The immediate 5'-flanking sequence contains several motifs which are characteristic of upstream regions including a TATA box, a CAAT box, a sequence similar to that recognized by transcription factor AP-1 and a purine-rich sequence resembling that found upstream in all other lactoprotein genes. Other possible regulatory sequences are found upstream of exon 4. 3. The organization of the kappa-casein gene, together with its upstream sequence, confirms previous conclusions that it is unrelated to the calcium-sensitive-casein gene family to which it is linked. Evidence is presented which supports a previous suggestion that kappa-casein and the fibrinogens are evolutionarily related. 4. Intron sequences contain several examples of the A family of the artiodactyl Alu-like repeated sequences, together with a single example of a C-family sequence. The remainders of the introns of the kappa-casein gene, compared with the repeat elements and exons, are A + T-rich. 5. Among the lambda clones isolated, representatives were found of the A and B genetic variants which can be distinguished by restriction-enzyme analysis. Several other examples of polymorphisms in the non-coding region were found.
Eur J Biochem 1988 Dec 15
PMID:Isolation and characterization of the bovine kappa-casein gene. 320 64


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