Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary mouse brain astrocytes were stimulated with phorbol 12-myristate 13-acetate (PMA), serum, forskolin and ionophore A23187, in order to investigate the effect of distinct signalling pathways on the expression of the nerve growth factor (NGF) gene and of proto-oncogenes encoding transcription factors of the Fos and Jun families. PMA, and to a lesser extent serum, induced a marked accumulation of NGF transcripts, in agreement with published observations [Brain Res., 570 (1992) 316-322]. The effect of A23187 was less pronounced and that of forskolin barely detectable. No relationship was observed between the expression of NGF gene and that of c-fos, fos-B, fra-1, jun-B proto-oncogenes. In contrast, changes in the levels of NGF transcripts were associated with corresponding modifications of the levels of c-jun transcripts, a fact which suggests that the c-Jun protein exerts a regulatory role on the expression of the NGF gene. In these cells, however, the regulation of NGF synthesis appears complex, since a pretreatment with forskolin or ionophore A23187 interfered with the promoting effect elicited by PMA or serum in inducing an early decline of the levels of NGF transcripts. This phenomenon was accompanied by a corresponding decrease in the amounts of cell-secreted NGF in cells treated with forskolin and PMA. A23187 had a much more striking effect on the production of mature NGF since this compound maintained the level of cell-secreted NGF to basal values, irrespective of the presence of PMA. A similar inhibitory effect was observed with thapsigargin, another compound able to increase the cytosolic concentration of calcium.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interactions between second messenger pathways influence NGF synthesis in mouse primary astrocytes. 774 33

Induction of phase 2 detoxification enzymes by phenolic antioxidants can account for prevention of tumor initiation but cannot explain why these compounds inhibit tumor promotion. Phase 2 genes are induced through an antioxidant response element (ARE). Although the ARE resembles an AP-1 binding site, we show that the major ARE binding and activating protein is not AP-1. Interestingly, AP-1 DNA binding activity was induced by the phenolic antioxidant tert-butylhydroquinone (BHQ), but the induction of AP-1 transcriptional activity by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) was inhibited by this compound. BHQ induced expression of c-jun, junB, fra-1, and fra-2, which encode AP-1 components, but was a poor inducer of c-fos and had no effect on fosB. Like c-Fos and FosB, the Fra proteins heterodimerize with Jun proteins to form stable AP-1 complexes. However, Fra-containing AP-1 complexes have low transactivation potential. Furthermore, Fra-1 repressed AP-1 activity induced by either TPA or expression of c-Jun and c-Fos. We therefore conclude that inhibitory AP-1 complexes composed of Jun-Fra heterodimers, induced by BHQ, antagonize the transcriptional effects of the tumor promoter TPA, which are mediated by Jun-Fos heterodimers. Since AP-1 is an important mediator of tumor promoter action, these findings may explain the anti-tumor-promoting activity of phenolic antioxidants.
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PMID:Antitumor promotion by phenolic antioxidants: inhibition of AP-1 activity through induction of Fra expression. 776 34

Moloney murine leukemia virus (Mo-MuLV) is a thymotropic and leukemogenic retrovirus which causes T lymphomas. The long terminal repeat (LTR) of Mo-MuLV affects the regulation of a number of cellular genes, including collagenase IV, monocyte chemoattractant protein-1, and c-jun genes, all of which contain 12-O-tetradecanoylphorbol-13-acetate-responsive element consensus sites within their promoters. We report here that Mo-MuLV stimulates the collagenase IV gene through transcription factor AP-1, and that the expression of a subgenomic portion of Mo-MuLV LTR alone is sufficient for this effect. Transient or stable expression of the viral LTR increases cellular AP-1 DNA binding activity. The collagenase IV 12-O-tetradecanoylphorbol-13-acetate-responsive element consensus sequence was shown to be required for this trans-activation. Deletions or mutations of this consensus site which abolished AP-1 binding also abolished trans-activation by the LTR. Transient or stable transfection of the viral LTR into cells stimulated c-jun gene expression, suggesting one mechanism whereby the viral LTR may induce cellular AP-1 activity. Thus, the Mo-MuLV LTR, through activation of the transcription factor AP-1, is capable of regulating cellular gene expression, including the induction of proto-oncogenes. This activity may be relevant to the mechanisms whereby retroviruses which do not contain oncogenes induce neoplasia.
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PMID:The Moloney leukemia retroviral long terminal repeat trans-activates AP-1-inducible genes and AP-1 transcription factor binding. 777 15

Retinoic acid receptors (RARs) regulate gene expression either by directly binding to the RAR-responsive elements or by antagonizing the action of c-Jun/c-Fos (AP1). AP1 is involved in the expression of metalloproteases, cytokines and other factors which play critical roles in the turnover of extracellular matrix, inflammation and hyperproliferation in diseases such as psoriasis, rheumatoid arthritis and in tumor metastases. We demonstrate here that synthetic retinoids inhibit 12-O-tetradecanoylphorbol-14-acetate-induced transcription from the stromelysin AP1 motif through RAR alpha, -beta, and -gamma. Interestingly, these diaryl acetylenic retinoids, which are potent agonists only for RAR beta and RAR gamma, but not for RAR alpha, in transactivation assays, are able to inhibit AP1-dependent gene expression through RAR alpha. Thus these analogs can differentially affect the transactivation and AP1 antagonistic functions of RAR alpha. These results demonstrate that the transactivation and AP1 antagonistic functions are separable, and it should be possible to develop retinoids that are completely specific for AP1 antagonism through all RARs. Furthermore, using an RAR-selective ligand, we also demonstrate the separation of ligand binding and AP1 antagonism functions of RARs.
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PMID:Separation of transactivation and AP1 antagonism functions of retinoic acid receptor alpha. 782 31

The functional induction of c-fos in the sodium butyrate-induced differentiation of F-98 glioma cells was studied. Fos protein level was increased by butyrate. In contrast, c-Jun protein was constitutively expressed and was not affected by butyrate. Gel-retardation assay indicates Fos as a component of the complex formed between the consensus oligonucleotide of the TPA (PMA, phorbol 12-myristate 13-acetate) response element (TRE) and nuclear extract prepared from butyrate-treated cells. Transfection studies showed that butyrate increased transcription from a multimeric TRE-driven reporter construct, and the effect was mimicked by transfecting cells with fos-expression plasmid. Furthermore, under conditions of c-fos over-expression, transactivation by butyrate was essentially abolished. These data suggest that Fos induction had a functional role in gene activation. Characterization of stable c-fos transfectants demonstrated that these cells displayed alterations in morphology, showed serum-dependent growth, had slower growth rates and grew to lower saturation densities than did untransfected F-98 cells or transfected cells that did not express c-fos. Immunofluorescent staining indicated that fos transfectants also had elevated glial fibrillary acidic protein ('GFAP') expression. Transfection of the c-fos promoter-chloramphenicol acetyltransferase fusion gene into F-98 cells revealed that activation of c-fos by butyrate was exerted at the promoter level, and sequences located within nucleotides -757 to -402 of the c-fos promoter were responsible for butyrate induction. Our data indicate that transcriptional activation of c-fos through its promoter by butyrate resulted in increased Fos protein expression. Transfection studies show that both c-fos and butyrate activate TRE-containing genes, and fos may be a downstream mediator of butyrate. Furthermore, expression of c-fos plays a major role in modulating the growth properties of F-98 cells.
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PMID:Analysis of c-fos expression in the butyrate-induced F-98 glioma cell differentiation. 786 28

The ability of the glucocorticoid receptor (GR) to induce gene expression in embryonic chicken retinal tissue increases dramatically during development, although the quantity of the receptor molecules does not change greatly with age. This study examines the possible involvement of c-Jun in the developmental control of GR activity. Expression of c-Jun in retinal tissue was high at early embryonic ages and declined during development. Elevation of c-Jun expression in retina of mid-developmental ages by treatment with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), or by introduction of a c-Jun expression vector, caused a pronounced decline in the inducibility of the endogenous glutamine synthetase gene and the transiently transfected CAT constructs p delta G46TCO and pGS2.1CAT, that are controlled by a minimal consensus glucocorticoid response element (GRE) promoter and the glutamine synthetase promoter, respectively. The effect of c-Jun was dose dependent and could be reversed by overexpression of GR. C-Jun-evoked repression of GR activity could be relieved by overexpression of Jun D. Overexpression of Jun D could also elevate the responsiveness of early embryonic retina to glucocorticoids and cause a 5-fold increase in p delta G46TCO induction. The effect of Jun D could be reversed by overexpression of c-Jun. Expression of c-Jun might therefore be important for repression of GR activity at early embryonic ages.
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PMID:Involvement of c-Jun in the control of glucocorticoid receptor transcriptional activity during development of chicken retinal tissue. 790 25

Transcription of the rat tyrosine aminotransferase gene (TAT) is stimulated in liver by glucocorticoid hormones or by cAMP-increased protein kinase A activity via enhancers located 2.5 kilobases (kb) and 3.6 kb upstream of the start site of transcription. The proteins mediating induction have been characterized, and protein binding in the two enhancer regions has been analyzed in vivo and in vitro. The TAT gene is therefore a useful model system with which to study cross-talk between different signal transduction pathways. We find that activation of the second messenger pathway leading from protein kinase C to the transcription factor AP-1 by the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) impairs induction of the TAT gene both by glucocorticoid hormones and cAMP. The effects of TPA treatment on chromatin structure of the TAT gene and protein-DNA interactions in vivo were assayed. Under conditions in which TPA impairs glucocorticoid induction of TAT mRNA, the glucocorticoid receptor and other proteins binding within the glucocorticoid-inducible enhancer occupy their binding sites, indicating that inhibition occurs at a later step necessary for transcriptional stimulation. On the other hand, inhibition of cAMP induction correlates with reduced occupancy of the cAMP response element in vivo.
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PMID:Cross-talk modulation of signal transduction pathways: two mechanisms are involved in the control of tyrosine aminotransferase gene expression by phorbol esters. 791 48

The rat glutathione transferase P gene has a strong enhancer element, termed GPE I, which is composed of a dyad of palindromicly oriented TPA (phorbol 12-O-tetradecanoate 13-acetate) responsive element (TRE)-like sequences. TRE is a binding sequence of the transcription factor AP-1, which consists of several closely related proteins belonging to the Jun and Fos family. The gel retardation experiments show that all the heterodimers formed between the Jun and Fos related gene products bind to the GPE I as well as to the TRE. In spite of the fact that the GPE I has a stronger activity than the TRE, the binding affinities of these heterodimers to the GPE I are much lower than to the TRE. Co-transfection studies of the reporter construct containing the GPE I and expression constructs of each of the Jun and Fos family cDNAs indicate that FosB and delta FosB repress transcription through the GPE I enhancer. These results suggests that some of Jun/Fos family may regulate the rat GST-P gene expression through the GPE I in vivo.
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PMID:Jun and Fos related gene products bind to and modulate the GPE I, a strong enhancer element of the rat glutathione transferase P gene. 791 48

Evi-1 is a gene, encoding a zinc finger protein, associated with a common viral integration site in murine leukemias. It is suggested that Evi-1 plays important roles in embryogenesis and transformation of myeloid cells. To elucidate mechanisms by which Evi-1 induces such biological effects, we analyzed the relationship between Evi-1 and AP-1 which could regulate cellular proliferation and differentiation. When Evi-1 was expressed, transactivation through a 12-O-tetradecanoylphorbol 13-acetate-responsive element was observed in NIH3T3 and P19 cells. Evi-1-transfected P19 cells showed some differentiated phenotypes and increased expression of endogenous c-Jun and c-Fos. These results indicate that Evi-1 raises AP-1 activity. Evi-1 caused stimulation of the c-fos promoter transactivation, which seems to be a main mechanism of AP-1 activation, through at least two portions of the promoter. Evi-1 has the first zinc finger domain at the N terminus and the second zinc finger domain near the C-terminus. We constructed deletion mutants of Evi-1 and investigated the functions of these domains. It was shown that the second zinc finger domain is essential for the activation of AP-1 and transactivation of the c-fos promoter.
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PMID:Evi-1 raises AP-1 activity and stimulates c-fos promoter transactivation with dependence on the second zinc finger domain. 792 53

Tumor necrosis factor alpha (TNF alpha) has multiple biological functions including the prolonged activation of the collagenase and c-jun genes, which are regulated via their AP-1 binding sites. We show that incubating human fibroblasts with TNF alpha induces prolonged activation of JNK, the c-Jun kinase, which phosphorylates the transactivation domain of c-Jun. Furthermore, an immune complex kinase assay specifically demonstrates that TNF alpha stimulates the activity of JNK1, the recently described predominant form of JNK. TNF alpha also produces a small and transient increase in extracellular signal-regulated kinase (ERK) activity and no measured increase in Raf-1 kinase activity. On the other hand, epidermal growth factor causes a prolonged activation of Raf-1 kinase and ERK activity and a smaller, more transient activation of JNK, whereas the phorbol ester phorbol 12-myristate 13-acetate causes a small stimulation of Raf-1 kinase and a pronounced stimulation of ERK activity. The activation of JNK by TNF alpha does not correlate with Raf-1 or ERK activity. The kinetics of Raf-1, ERK, and JNK induction by epidermal growth factor, phorbol 12-myristate 13-acetate, or TNF alpha indicate distinct mechanisms of activation in human fibroblasts.
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PMID:Tumor necrosis factor alpha stimulates AP-1 activity through prolonged activation of the c-Jun kinase. 792 60


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