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

Neuronal stimulation can rapidly activate several immediate early genes that code for transcription factors. We have used primary cortical cultures to study the regulation of four of these genes, c-fos, c-jun, jun-B, and zif268. Immunocytochemical studies with antibodies to Jun-B, c-Jun, and c-Fos demonstrate intense staining in the nuclei of a subset of cortical neurons in mature cultures (21-25 days in vitro) but not young cultures (3-7 days in vitro). To assess whether this immunoreactivity may be induced by spontaneous synaptic activity that develops with a similar profile, we examined the effects of agents that reduce this synaptic activity. Tetrodotoxin or N-methyl-D-aspartate receptor antagonists suppress basal immunoreactivity to Jun-B and c-Fos, but not c-Jun, indicating that the basal level of c-Jun expression is not dependent on electrical activity. Picrotoxin, an agent that increases synaptic excitation indirectly by blocking inhibitory synaptic currents mediated by gamma-aminobutyric acidA receptors, markedly increases the percentage of neurons displaying immunoreactivity to c-Fos, c-Jun, Jun-B, and Zif268. Northern analysis suggests that the increases in immunostaining induced by picrotoxin are secondary to a rapid increase in mRNA for these proteins. These findings provide evidence for rapid transcriptional regulation of immediate early genes in cortical neurons by synaptic activity.
J Neurochem 1991 Dec
PMID:Synaptic regulation of immediate early gene expression in primary cultures of cortical neurons. 171 31

Recent advances indicate a link between tumour promoters, transformation, and AP-1 activity. Protein kinase C activation increases AP-1 DNA-binding activity independently of new protein synthesis. AP-1 is also stimulated by transforming oncoproteins and growth factors. These proteins are thought to participate in a signalling cascade affecting the nuclear AP-1 complex composed of the Jun and Fos proteins. Because c-Jun is the most potent transactivator in the AP-1 complex and is elevated in Ha-ras-transformed cells, in which c-Fos is downregulated, we focused on it as a potential target. c-Jun could convert input from an oncogenic signalling cascade into changes in gene expression. Indeed, transformation of rat embryo fibroblasts by c-Jun requires an intact transcriptional activation domain and cooperation with oncogenic Ha-ras. Expression of oncogenic Ha-ras augments transactivation by c-Jun and stimulates its phosphorylation. Here we describe the mapping of the Ha-ras-responsive phosphorylation sites to serines 63 and 73 of c-Jun. Site-directed mutagenesis indicates that phosphorylation of these serines is essential for stimulation of c-Jun activity and for cooperation with Ha-ras in ocogenic transformation.
Nature 1991 Dec 12
PMID:Oncogenic and transcriptional cooperation with Ha-Ras requires phosphorylation of c-Jun on serines 63 and 73. 174 29

Cell proliferation and phenotype of cells from female reproductive tissues are regulated by estrogens. It is therefore important to understand how estrogen action can be modulated. It recently has been reported that certain nuclear receptors can antagonize the tumor promoter 12-O-tetradeconylphorbol-13-acetate (TPA) by direct interaction with the transcription factor AP-1, and that the AP-1 constituents cJun and cFos can inhibit receptor activity. This mutual antagonism appears to be based on direct protein-protein interaction. In the human breast cancer cell line MCF-7, TPA leads to growth arrest and altered cell morphology. We have investigated here whether in MCF-7 cells and other cell lines AP-1 and estrogen receptors (ERs) can inhibit each other's activity. We find that TPA or the AP-1 components cJun and cFos can inhibit estradiol-dependent estrogen receptor activity in most cell lines investigated. In addition, ER mRNA is rapidly down-regulated in MCF-7 cells. Gel retardation experiments show that ER DNA binding is inhibited in vitro by cJun protein, while ER also can inhibit cJun DNA binding. However, in vivo we do not observe inhibition of AP-1 activity by ER in the cell lines investigated here. On the contrary, we observed an enhancing effect at low ER concentrations on AP-1. Together our data suggest a new regulatory pathway by which ER activity can be modulated by AP-1. Several mechanisms including ER-AP-1 protein interaction appear to be involved.
Mol Endocrinol 1991 Dec
PMID:Inhibition of estrogen receptor activity by the tumor promoter 12-O-tetradeconylphorbol-13-acetate: a molecular analysis. 179 43

Early induction of the mRNAs encoding the c-Fos and c-Jun nuclear proteins was examined in rat brain by in situ hybridization at various timepoints following global forebrain ischemia by the method of four-vessel occlusion. All animals were subjected to 20 min of transient ischemia. This produced a pattern of proto-oncogene activation that was most intense in the granule cells of the dentate gyrus 30 min after ischemia, while the hilar cells in the dentate and the pyramidal cells of the CA3 region in the hippocampus showed a more delayed but robust expression of these immediate early genes at 1 h. The neurons of the CA1 region exhibited a more moderate hybridization signal at 1-2 h postischemia. Very little hybridization signal for either immediate early gene could be detected in animals perfused with fixative immediately following ischemia, suggesting that cellular energy levels may have to be restored to a certain level before efficient de novo mRNA synthesis can occur. In the cerebellum, a similar temporal pattern was observed: the granule cells exhibited a prompt but patchy expression of c-fos and c-jun that was followed by a delayed signal in the Purkinje cells. Without exception c-fos and c-jun appeared to be expressed in unison, although the time course of c-fos and c-jun mRNA accumulation and decay was different in various brain regions: invariably the cerebellum returned rapidly to its baseline with virtually no remaining signal at 3 h postischemia, while c-fos and c-jun activation in the hippocampus remained high at 3 h and returned to baseline by 6 h. Several other brain regions showed early production of c-fos and c-jun mRNAs, such as the medial habenula, piriform cortex, the amygdala, the centromedian, lateral posterior, paracentral, intermediodorsal and reuniens nuclei of the thalamus and the ventromedial and dorsal nuclei of the hypothalamus; in the brainstem, the trapezoid body and the noradrenergic neurons of the locus ceruleus as well as the adrenergic neurons in the ventrolateral medulla (C1 group) and nucleus tractus solitarius (C2 group) regions displayed slightly less intense hybridization signals. In addition, the ependyma of the lateral ventricles and the third ventricle showed a prompt albeit short-lived production of c-fos and c-jun mRNAs. Sham-operated animals as well as animals that had survived to one week postischemia showed either no or only trace levels of hybridization signal.(ABSTRACT TRUNCATED AT 400 WORDS)
Brain Res 1991 Dec 20
PMID:In situ hybridization analysis of c-fos and c-jun expression in the rat brain following transient forebrain ischemia. 181 28

The adenovirus E1A protein stimulates transcription of various genes. Recent experiments using a fusion protein have shown that E1A can function through a specific CRE (cyclic AMP response element)-binding protein, CRE-BP1 (also designated ATF-2), which stimulates the transcription from a CRE-containing promoter by homodimer formation or heterodimer formation with c-Jun. In this paper, the functional domains required for mediation of the E1A-induced trans-activation were analyzed using deletion and point mutants of CRE-BP1. The mutation in the putative metal finger structure or leucine zipper structure completely abolished the ability of CRE-BP1 to mediate the E1A-induced trans-activation. Furthermore, overexpression of CRE-BP1 or c-Jun interfered with the E1A-induced trans-activation. These results suggest that the complete putative metal finger structure in the N-terminal region of CRE-BP1 plays an important role for the E1A-induced trans-activation, and the heterodimer of CRE-BP1 with the unidentified protein participates in the interaction with E1A.
J Biol Chem 1991 Dec 15
PMID:Complete putative metal finger and leucine zipper structures of CRE-BP1 are required for the E1A-induced trans-activation. 183 14

The genes of the Jun family encode components of the TPA-inducible transcription factor AP-1. These genes are induced by a wide variety of extracellular stimuli, such as growth factors, phorbol esters and activators of protein kinase A. We have previously shown that the adenovirus type 5 E1A protein (E1A5) induces c-jun and junB expression in a number of different cell types. In this paper we show that the third member of the Jun family, junD, is also strongly induced by E1A5. Multiple sequences in the junB and junD promoters are responsible for the effects of E1A5. By contrast, adenovirus type 12 E1A (E1A12), like retinoic acid (RA), strongly induces c-jun expression, while expression of junB and junD is not altered. Interestingly, E1A12 expression leads to complete differentiation of P19 EC cells, comparable to the effect of RA on these cells, while E1A5-expressing cells are only partially differentiated.
Oncogene 1991 Dec
PMID:Differential regulation of JunB and JunD by adenovirus type 5 and 12 E1A proteins. 183 51

We investigated the effect of c-Fos and/or c-Jun co-expression on transcription activation by the progesterone (PR), glucocorticoid (GR) or androgen (AR) receptors using three different reporter genes and four different cell lines. We found that c-Fos could only inhibit, while c-Jun could either inhibit or further stimulate receptor-induced transcription. All these effects were receptor, promoter, and cell type specific, and, importantly, the steroid receptors had non-reciprocal effects on the transactivation ability of c-Jun in the presence or absence of c-Fos. Collectively, these results argue against heterodimer formation as a mechanism to explain the phenomena. Transactivation by the endogenous PR in T47D cells could be inhibited by increasing the intracellular c-Fos level with forskolin as well as by co-expressing c-Fos; no such effect was seen in MCF-7 cells. The inhibition by c-Fos of PR-induced transcription involves a competitive mechanism, which requires the presence of the intact c-Fos leucine zipper and is directed mainly at the transcription activation function (TAF) located in the PR and GR hormone binding domains (TAF-2). However, the co-expression of c-Fos did not alter the 'squelching/transcriptional interference' by the PR of estrogen receptor (ER)-induced transcription. Multiple mechanisms are discussed which may be involved in the crosstalk between the two signal transduction pathways.
EMBO J 1991 Dec
PMID:Cell-specific inhibitory and stimulatory effects of Fos and Jun on transcription activation by nuclear receptors. 193 3

An intragenic enhancer in the pol gene of human immunodeficiency virus type 1 has previously been identified (Verdin et al., Proc. Natl. Acad. Sci. USA 87:4874-4878, 1990). This element is composed of two subdomains both exhibiting phorbol ester-inducible enhancing activity on the viral thymidine kinase promoter in HeLa cells. Examination of the nucleotide sequence of one of these domains (nucleotides 4079 to 4342, HXB2 isolate) revealed the presence of three short DNA regions highly homologous to the recognition site for cellular transcription factor AP-1. Two short oligonucleotides containing these AP-1 sites each functioned as a phorbol ester-inducible enhancer when cloned upstream of the thymidine kinase promoter and transfected into HeLa cells. Gel mobility shift assays and competition experiments using the same two oligonucleotides demonstrated that they bound affinity-purified AP-1 or AP-1 present in uninduced and 12-O-tetradecanoylphorbol-13-acetate-induced HeLa nuclear extracts. Footprinting experiments confirmed that all three predicted sites bound purified AP-1. These results suggest that the AP-1 factor could play a role in the transcriptional regulation of human immunodeficiency virus type 1 gene expression.
J Virol 1991 Dec
PMID:The intragenic enhancer of human immunodeficiency virus type 1 contains functional AP-1 binding sites. 194 59

Many essential biological pathways, including cell growth, development, and metabolism, are regulated by thyroid hormones (THs). TH action is mediated by intracellular receptors that belong to a large family of ligand-dependent transcription factors, including the steroid hormone and retinoic acid receptors. So far it has been assumed that TH receptors (TRs) regulate gene transcription only through the classical protein-DNA interaction mechanism. Here we provide evidence for a regulatory pathway that allows cross-talk between TRs and the signal transduction pathway used by many growth factors, oncogenes, and tumor promoters. In transient transfection studies, we observed that the oncogenes c-jun and c-fos inhibit TR activities, while TRs inhibit induction of the c-fos promoter and repress AP-1 site-dependent gene activation. A truncated TR that lacks only 17 amino acids from the carboxy terminus can no longer antagonize AP-1 activity. The cross-regulation between TRs and the signal transduction pathway appears to be based on the ability of TRs to inhibit DNA binding of the transcription factor AP-1 in the presence of THs. The constituents of AP-1, c-Jun, and c-Fos, vice versa, can inhibit TR-induced gene activation in vivo, and c-Jun inhibits TR DNA binding in vitro. This novel regulatory pathway is likely to play a major role in growth control and differentiation by THs.
Mol Cell Biol 1991 Dec
PMID:Novel pathway for thyroid hormone receptor action through interaction with jun and fos oncogene activities. 194 74

The nuclear phosphoprotein c-Jun, encoded by the proto-oncogene c-jun, is a major component of the AP-1 complex. A potent transcriptional regulator, c-jun is also able to transform normal rat embryo cells in cooperation with an activated c-Ha-ras gene. By deletion analysis, we identified the regions of c-Jun encoding transformation and transactivation functions. Our studies indicate that there is a direct correlation between the ability of the c-Jun protein to activate transcription and cotransform rat embryo cells. The regions involved in these functions include the conserved leucine zipper/DNA binding domain and an effector domain near its N terminus. This N-terminal region spans amino acids 61 to 146 of the c-Jun protein and is highly conserved among all Jun family members. These results support the hypothesis that c-Jun transforms cells by stimulating the expression of transformation-mediating genes.
Mol Cell Biol 1991 Dec
PMID:The transactivating domain of the c-Jun proto-oncoprotein is required for cotransformation of rat embryo cells. 194 89


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