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)

Transcription mechanisms regulating nerve growth factor (NGF) gene expression in the CNS are yet to be thoroughly understood. We have used C6-2B rat glioma cells to characterize the signal transduction pathways that contribute to transcriptional and posttranscriptional regulation of NGF mRNA. Because the NGF promoter contains an AP-1 consensus sequence, we have investigated whether increases in AP-1 binding activity correlate with enhanced NGF mRNA expression. Gel mobility shift assays using an oligonucleotide homologous to the AP-1 responsive element of the rat NGF gene (AP-1NGF) revealed that 12-O-tetradecanoyl phorbol-13-acetate (TPA) and, to a lesser extent, isoproterenol (ISO) and thapsigargin, a microsomal Ca(2+)-ATPase inhibitor, stimulated binding to AP-1NGF within 2 h. All of these stimuli increased NGF mRNA levels within 3 h. Cycloheximide pretreatment blocked the TPA and ISO-mediated binding to AP-1NGF suggesting that de novo synthesis of c-Fos/c-Jun may be required for the transcriptional regulation of NGF gene. Nuclear run-on assays and NGF mRNA decay studies revealed that TPA increases NGF transcription whereas ISO affects both transcription and mRNA stabilization. We propose that (i) different signal transduction mechanisms regulate the expression of the NGF gene in cells derived from the CNS, and (ii) both mRNA transcription and stability account for the cAMP-mediated increase in NGF mRNA levels.
Brain Res Mol Brain Res 1996 Jan
PMID:Correlation between increased AP-1NGF binding activity and induction of nerve growth factor transcription by multiple signal transduction pathways in C6-2B glioma cells. 871 34

Immunohistochemistry to Bcl-2, Bax, c-Myc, c-Fos, Fos-related, c-Jun, Jun B and Jun D was used to study the involvement of these factors in ionizing radiation-induced apoptosis in the cerebellum of the developing rat. Selective c-Jun overexpression was observed during the whole process of radiation-induced cell death. Furthermore, c-Jun overexpression was restricted to apoptotic cells, as shown by double labeling with the method of in situ labeling of nuclear DNA fragmentation and c-Jun immunohistochemistry. This is the first in vivo evidence that selective c-Jun overexpression is associated with apoptotic cell death in the developing nervous system following ionizing radiation.
Brain Res Mol Brain Res 1996 May
PMID:Selective c-Jun overexpression is associated with ionizing radiation-induced apoptosis in the developing cerebellum of the rat. 873 72

Several astrocyte gene products, such as enkephalin and glial fibrillary acidic protein (GFAP), are expressed at higher levels under in vitro conditions relative to in vivo. We have observed that cultured glial cells express high basal levels of transcription factors, such as fos-related antigens (Fra), c-Jun, JunD, and cAMP responsive element binding protein (CREB). When neuronal cells are plated on top of the monolayers, the expression of Fra, c-Jun, JunD, and GFAP decreases in the astroglial cells. The DNA binding activity to the AP-1-like sites of the GFAP and proenkephalin genes was examined in these cultures. The protein complex from glial cultures which recognizes the GFAP AP-1 element contained Fra immunoreactivity while the DNA binding from mixed neuronal/glial cultures consists of CREB-immunoreactive proteins. In glial cultures, no binding occurred to the proenkephalin AP-1-like element but a CREB-immunoreactive complex recognized this sequence in the mixed cultures. Thus, with the addition of neurons, both transcription factors and target gene products decrease in astroglial cells. The proteins that compose gene modulatory complexes also change suggesting that regulation of astroglial gene expression is modulated by neurons.
Brain Res Mol Brain Res 1996 Apr
PMID:Transcription factors in primary glial cultures: changes with neuronal interactions. 873 55

The dopamine receptor antagonist, haloperidol, produced a time-dependent differential induction of inducible transcription factors (ITFs) in rat striatal neurons: Fos, Fos B, Jun B, Jun D, Krox 20, and Krox 24, but not c-Jun, were induced in the caudate putamen and nucleus accumbens with varying time courses. The induction of Fos by haloperidol was stronger in anterior versus posterior regions of the striatum. In contrast, induction of Fos by the muscarinic agonist pilocarpine was stronger in the posterior regions of the striatum suggesting that muscarinic receptors do not play a role in the induction of ITFs in striatal neurons by haloperidol. Although c-Jun was not induced in caudate neurons by haloperidol it was strongly induced in these neurons following prolonged seizure activity. The differential pattern of Jun protein expression suggests that haloperidol induces a specific transcriptional program in basal ganglia neurons. These effects of haloperidol may be involved in producing its extrapyramidal side effects.
Brain Res Mol Brain Res 1995 Dec 28
PMID:Differential expression of inducible transcription factors in basal ganglia neurons. 875 Aug 32

Oxygen radicals are induced under various pathologic conditions associated with neovascularization. Oxygen radicals modulate angiogenesis in cultured human microvascular endothelial cells by an unknown mechanism. Treatment of human microvascular endothelial cells for 15 min with 0.1 to 0.5 mM hydrogen peroxide (H2O2) or 100 U of tumor necrosis factor alpha per ml induced tubular morphogenesis in type I collagen gels. Gel shift assays with nuclear extracts demonstrated that H2O2 increases the binding activities of two transcription factors, NF-kappaB and AP-1, but not of Spl. Tumor necrosis factor alpha increased the binding activities of all three factors. A supershift assay with specific antibodies against JunB, JunD, and c-Jun (Jun family) showed that the antibody against c-Jun supershifted the AP-1 complex after H2O2 treatment. Coadministration of the antisense sequence of NF-kappaB inhibited H2O2-dependent tubular morphogenesis, and the antisense c-Jun oligonucleotide caused partial inhibition. The angiogenic factor responsible for H2O2-induced tubular morphogenesis was examined. Cellular mRNA levels of vascular endothelial growth factor and interleukin-8 (IL-8), but not those of transforming growth factor alpha, were increased after treatment with 0.5 mM H2O2. Coadministration of anti-IL-8 antibody inhibited tubular morphogenesis enhanced by H2O2, and IL-8 itself also enhanced the formation of tube-like structures. Treatment with antisense NF-kappaB oligonucleotide completely blocked H2O2-dependent IL-8 production by endothelial cells. The tubular morphogenesis of vascular endothelial cells after treatment with oxidative stimuli and its possible association with NF-kappaB and IL-8, is examined.
Mol Cell Biol 1996 Aug
PMID:Involvement of the transcription factor NF-kappaB in tubular morphogenesis of human microvascular endothelial cells by oxidative stress. 875 23

ras is an important oncogene in experimental animals and humans. In addition, activated ras proteins are potent inducers of the transcription factor AP-1, which is composed of heterodimeric complexes of Fos and Jun proteins. Together with the fact that deregulated expression of some AP-1 proteins can cause neoplastic transformation, this finding suggests that AP-1 may function as a critical ras effector. We have tested this hypothesis directly by analyzing the response to activated ras in cells that harbor a null mutation in the c-jun gene. The transcriptional response of AP-1-responsive genes to activated ras is severely impaired in c-jun null fibroblasts. Compared with wild-type cells, the c-jun null cells lack many characteristics of ras transformation, including loss of contact inhibition, anchorage independence, and tumorigenicity in nude mice; these properties are restored by forced expression of c-jun. Rare tumorigenic variants of ras-expressing c-jun null fibroblasts do arise. Analysis of these variants reveals a consistent restoration of AP-1 activity. The results provide genetic evidence that c-jun is a crucial effector for transformation by activated ras proteins.
Mol Cell Biol 1996 Aug
PMID:Cellular transformation and malignancy induced by ras require c-jun. 875 51

Recent studies have shown that corticotropin releasing factor (CRF) stimulates c-fos gene expression in the AtT-20 corticotroph cell line, and that overexpression of c-Fos results in activation of POMC gene transcription. Since transactivation by c-Fos requires dimerization with a Jun family member to form the active transcription factor AP-1, we have examined the expression of multiple fos and jun related genes and have correlated their expression with AP-1 DNA binding activity in AtT-20 nuclear extracts after stimulation with CRF. Although basal expression of c-fos mRNA was extremely low, it was rapidly and transiently stimulated in AtT-20 cells following administration of either constant or a single pulse of CRF. In contrast, basal expression of c-jun mRNA was slightly higher and underwent little or no change in response to CRF. Specific ribonuclease protection analysis showed that in addition to c-fos, mRNA transcripts encoding fos B and jun B were rapidly stimulated in response to CRF, though levels of induced fos B mRNA were 20-40 times lower than c-fos or jun B, respectively. Gel shift analysis demonstrated that CRF caused a sustained increase in AP-1 DNA binding to both a canonical AP-1 element as well as to the POMC exon-1 AP-1 site. Studies with specific antisera directed against c-Fos revealed that although no c-Fos could be detected in AP-1 complexes in basal cell extracts, c-Fos became a prominent component of AP-1 following CRF stimulation, reaching maximal levels by 4 h. Despite the fact that AP-1 DNA binding activity remained elevated for at least 24 h after CRF, c-Fos was most prominent during the early phase of the response. Similarly, JunB was shown to be a major component of AP-1 DNA binding activity in CRF-stimulated AtT-20 nuclear extracts that persisted for at least 24h after stimulation. Despite the obvious induction of fos B mRNA in response to CRF, FosB protein was not detected in DNA bound AP-1 complexes. These data demonstrate that CRF is a potent stimulus for corticotroph expression of c-fos, jun B and fos B, and suggest that the subsequent increase in AP-1 may play a role in activation of gene expression and/or as a modulator of glucocorticoid receptor function.
Mol Cell Endocrinol 1996 May 17
PMID:CRF stimulates expression of multiple fos and jun related genes in the AtT-20 corticotroph cell. 879 51

The presence of the typical transcription factors c-Jun, c-Fos and cAMP-responsive element (CRE)-binding protein in the porcine anterior pituitary was examined by molecular cloning and their involvement in the membrane signal cascade, especially their roles in gonadotropin-releasing hormone (GnRH) stimulation, were studied. Several cDNA clones were isolated from a porcine anterior pituitary cDNA library using cDNA probes. They were identified as porcine c-jun and c-fos by determining their nucleotide sequences, but a homologue for CREB341 which is a member of CRE-binding protein was not detected in porcine anterior pituitary. Reverse transcription-polymerase chain reaction (RT-PCR) analysis was performed to estimate the c-jun and c-fos mRNA contents in GnRH-, forskolin- (cAMP activator) and tetradecanoyl phorbol acetate- (TPA; protein kinase C activator) treated primary cultures of porcine anterior pituitary cells. Densitometric quantification demonstrated that GnRH and TPA treatment increased c-jun and c-fos mRNA levels significantly, whereas forskolin reduced the levels of both. Therefore, c-Jun and c-Fos are definitely present in porcine anterior pituitary and their mRNAs differentially involved in the signal transduction pathway mediated by two kinases. In particular, GnRH might regulate gonadotropin expression by increasing of c-jun and c-fos levels.
Mol Cell Endocrinol 1996 May 17
PMID:Molecular cloning of c-jun and c-fos cDNAs from porcine anterior pituitary and their involvement in gonadotropin-releasing hormone stimulation. 879 56

In Syrian hamster liver, treatment with 3-methylcholanthrene (3-MC) markedly induces an isozyme of cytochrome P450 (CYP), CYP2A8. To elucidate the mechanism of this induction, we studied the effect of okadaic acid (OA), an inhibitor of serine threonine protein phosphatases 1 and 2A, on 3-MC-induced CYP2A8 expression in primary cultures of Syrian hamster hepatocytes. The addition of OA to the cultured hepatocytes at a concentration of 1 nM potentiated 3-MC- (0.1 and 1 microM) induced expression of mRNA and protein of CYP2A8 and its associated coumarin 7-hydroxylase activity. In addition, OA not only induced c-fos and jun-D mRNA, components of transcription factor activator protein-1 (AP-1), with an increase in AP-1 binding activity in the nucleus, but also activated AP-1-dependent gene transcription in the hepatocytes. The dose-dependent effect of OA on 3-MC-induced CYP2A8 expression corresponded to that of OA on c-fos and jun-D mRNA induction and on the activation of AP-1-dependent gene transcription. The expression of c-fos and jun-D mRNA induced by OA preceded the expression of CYP2A8 mRNA potentiated by co-treatment with 3-MC and OA. Treatment with anisomycin and cycloheximide also potentiated 0.1 microM 3-MC-induced coumarin 7-hydroxylase activity, induced c-fos and jun-D mRNA expression, and activated AP-1-dependent gene transcription in the hepatocytes. Furthermore, 3-MC-induced CYP2A8 expression was potentiated in the hepatocytes transfected with c-Jun expression plasmid. These results suggest that AP-1, inducible by serine threonine protein kinase, may be one of the components of the signal transduction system from 3-MC to CYP2A8 gene expression.
Mol Pharmacol 1996 Sep
PMID:Okadaic acid potentiates 3-methylcholanthrene-induced CYP2A8 gene expression in primary cultures of Syrian hamster hepatocytes: possible involvement of activator protein-1. 879 94

Immediate early gene products (c-fos, c-jun and their cognates) act as transcription factors coupling physiologically relevant stimuli to long-term responses by binding to the AP-1 site in the promoter region of target genes. The induction of c-fos has been identified in the paraventricular (PVN) and supraoptic (SON) hypothalamic magnocellular nuclei after hyperosmotic stimulation by using in situ hybridization and immunocytochemistry. In this study, AP-1 DNA binding activity, an indicator of the functional form of the c-fos transcription factor, was examined in nuclear extracts prepared from these brain regions using an electrophoretic mobility shift assay and a labeled oligonucleotide containing the AP-1 consensus sequence. Two hours after hypertonic saline injection (i.p.), rats were killed and nuclear proteins were extracted from tissue punches of brain regions to assess AP-1 binding activity. Hyperosmolality induced an increase of AP-1 binding activity in nuclear protein from SON and PVN, but not striatum. This binding was competitively displaced by excess unlabeled AP-1 oligonucleotide whereas addition of increasing amounts of unlabeled SP-1 oligonucleotide (promoter site on housekeeping genes for the ubiquitous SP-1 transcription factor) did not decrease the binding. The binding protein was shown to contain c-Fos/Fra and c-Jun since addition of c-Fos/Fra antiserum formed a supershift of the DNA, protein and antibody complex, and c-Jun antibody blocked the protein DNA binding. These data suggest that hyperosmolality leads to a selective and specific increase in AP-1 DNA binding activity which may be responsible for regulating secondary target gene expression in the hypothalamic SON and PVN.
Brain Res Mol Brain Res 1996 Jul
PMID:AP-1 DNA binding activity induced by hyperosmolality in the rat hypothalamic supraoptic and paraventricular nuclei. 880 19


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