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

The regulation of jun family genes and AP1 activity during the course of differentiation of F9 embryonal carcinoma stem cells was investigated. The induction of differentiation by retinoic acid (RA) leads to an accumulation of c-jun mRNA caused by increased c-jun transcription. This induction is an indirect response to RA and requires a functional AP1 binding site within the c-jun promoter. Expression of jun-B mRNA, however, is transiently induced but at a later time point is repressed by RA. The third member of the family, jun-D, is already active in undifferentiated cells and is only slightly induced after differentiation. Differentiation also converts c-jun from being refractory to phorbol esters to a highly inducible state. The development of this response is correlated with increased AP1 activity in RA-treated cells. By contrast, the induction of c-fos by phorbol esters or cAMP is greatly diminished after RA treatment. Transfection experiments indicate that, in the absence of c-Fos, only c-Jun is an effective transactivator. Hence, the major increase in AP1 activity is due to elevated c-jun expression and probably involves positive autoregulation by the c-Jun protein. Furthermore, these results demonstrate that AP1 activity can be stimulated by phorbol ester without concomitant c-fos induction. Forced expression of c-Jun and v-Jun results in activation of at least two differentiation marker genes, EndoB and tissue plasminogen activator, whose regulatory regions contain AP1 binding sites. Thus, the induction of c-jun transcription by RA, although indirect, can have an important role in the differentiation process.
 ...
PMID:Elevation of AP1 activity during F9 cell differentiation is due to increased c-jun transcription. 196 81

The protooncogene c-jun encodes a component of the transcription factor AP-1. Both murine c-jun and a related gene (jun-B) are rapidly activated in BALB/c3T3 cells by serum growth factors. We report here the cloning and analysis of a cDNA encoding a third member of the murine jun family, jun-D. The amino acid sequence encoded by jun-D has two extensive regions of homology with the other Jun proteins. One homology region includes the DNA-binding domain and sequences required for dimer formation and interaction with the Fos oncoprotein; the other includes the acidic sequence thought to be involved in gene activation. All three jun mRNAs are present in a variety of murine tissues and cell lines. In resting 3T3 cells, jun-D is expressed at a higher level compared to c-jun and jun-B, and its transcription is stimulated only slightly by serum growth factors. Thus, jun-D appears to be regulated differently than c-jun and jun-B.
 ...
PMID:jun-D: a third member of the jun gene family. 249 44

In an extensive screen of a cDNA library prepared from serum-stimulated mouse NIH 3T3 cells, we identified three distinct jun-related clones. Two of them were carrying c-jun and junB sequences respectively, whereas the sequence of the third group of clones (junD) was distinct from these two and from v-jun. The amino acid sequences derived from these jun-related clones are very well conserved in five distinct regions including the putative DNA binding domain. Truncated c-Jun and JunD proteins containing the C-terminus recognize the same DNA sequences which were defined as the PEA1/AP1 binding sequence or TPA response element (TRE). Furthermore, both can trans-activate a promoter including the TRE, and this activation is further enhanced by c-fos. Contrary to c-jun and junB transcription, which are strongly stimulated by serum or TPA treatment of quiescent 3T3 cells, junD transcription is not significantly stimulated in these conditions. The tissue distribution and levels of expression of junD mRNA differ from that of c-jun and junB mRNA. These observations suggest that each of these Jun-related gene products has a distinct role in the control of gene activity and growth in the organism.
 ...
PMID:Characterization of junD: a new member of the jun proto-oncogene family. 250 80

The effect of a single injection of caffeine on the expression of c-fos, c-jun, junB, and junD, on activator protein 1 (AP-1) and on the levels of preproenkephalin mRNA in rat striatum was studied. Male rats were given caffeine (25 mg/kg, 50 mg/kg, or 100 mg/kg, i.p.) and sacrificed at different times (0.5, 1, 2, 4, or 8 hr) after administration. By using in situ hybridization of adjacent sections we found a rapid, transient, and dose-dependent increase of c-fos, c-jun, and junB by caffeine in striatum, especially in the lateral part. The induction peaked after 1 hr, but persisted for 2 hr, and in the case of junB for 4 hr. No induction of junD was found. A strong induction of junB, a weak induction of c-fos and c-jun, but not of junD, was seen in nucleus accumbens. Furthermore, by using gel shift assay we found an induction of AP-1 by caffeine (100 mg/kg) in striatum, which peaked 2 hr after administration and was clearly increased after 4 hr. c-Fos, c-Jun, and JunB proteins were components of the AP-1. There was also a dose-dependent induction of preproenkephalin mRNA, which was most pronounced in the lateral and caudal part of striatum; the level peaked 4 hr after injection and was still significantly increased after 8 hr. In a complementary study we could not find increased binding to the AP-1-like site in the 5'-flanking sequence of proenkephalin following caffeine treatment. The data show that a single dose of caffeine induces a temporally and spatially characteristic pattern of c-fos, c-jun, and junB induction, followed by changes in AP-1 and preproenkephalin mRNA. Thus, a single dose of caffeine causes changes in gene transcription in the brain that may be related to the adaptive changes that occur after caffeine administration. However, a direct causal link between the immediate early genes and enkephalin could not be proven.
 ...
PMID:Increased expression of c-jun, junB, AP-1, and preproenkephalin mRNA in rat striatum following a single injection of caffeine. 775 31

Okadaic acid (OA) is a novel, non-phorbol ester-type tumor promoter, which is a specific inhibitor of protein phosphatases 1 and 2A. Treatment of human fibrosarcoma HT-1080 cells with OA resulted in induction of collagenase and stromelysin-1 mRNA levels, while mRNA levels for tissue inhibitor of metalloproteinases-1 were enhanced to a lesser extent. Induction of collagenase and stromelysin-1 mRNA levels was dependent on protein synthesis. Exposure of HT-1080 cells to OA resulted in marked and persistent induction of junB, junD, and c-fos mRNA levels up to 24 h, while c-jun mRNA levels were only slightly elevated. In transiently transfected HT-1080 cells, OA-elicited activation of a 3.8-kilobase collagenase promoter/reporter gene construct was entirely dependent on junB expression, as determined by cotransfection with a junB antisense expression construct. Overexpression of JunB in HT-1080 cells enhanced collagenase promoter activity by 10-fold, and OA augmented trans-activation of collagenase promoter by c-Jun and JunB. The results indicate that induction of collagenase gene expression by OA is mediated by enhanced JunB expression, as well as enhanced trans-activating capacity of AP-1 complexes containing c-Jun and JunB. These results also suggest that selective overexpression of junB may enhance invasive and metastatic potential of neoplastic cells.
 ...
PMID:Okadaic acid-elicited transcriptional activation of collagenase gene expression in HT-1080 fibrosarcoma cells is mediated by JunB. 784 22

We have studied the expression of the c-jun gene during dimethyl-sulfoxide (DMSO) induced differentiation of Friend erythroleukemia (F-MEL) cells. No expression of c-jun was detected in a differentiation-competent F-MEL cell line (745A) either before or after treatment with DMSO. By contrast, c-jun expression was constitutive in a F-MEL cell line (TFP10) resistant to DMSO-induced differentiation and increased with DMSO. We have investigated the possible role of c-jun in conferring this resistance by stably transfecting either sense or antisense c-jun constructs into both differentiation-sensitive 745A and defective TFP10 cell lines. Inhibition of c-jun expression by antisense transcripts in the TFP10 cells restored their ability to undergo erythroid differentiation when exposed to DMSO while expression of junB or junD antisense vectors failed to do so. In addition, c-jun overexpression in the 745A cells resulted in decreased DMSO-induced differentiation. These results indicate a correlation between the level of c-jun expression and the ability of F-MEL cells to undergo DMSO-induced differentiation and suggest that c-Jun may be an important negative regulator in this process.
 ...
PMID:Antisense c-jun overcomes a differentiation block in a murine erythroleukemia cell line. 820 42

Among the murine Jun family of transcription factors, c-Jun and JunD are closely-related proteins with similar dimerization, DNA binding and transactivating properties. However, when expressed from a self-replicating retroviral RCAS vector, c-jun, but not junD, transforms chick embryo fibroblasts. We attempted to map the regions of c-jun which are important for transformation by constructing hybrids between c-jun and junD. Using common restriction sites, we prepared six different chimeric molecules. All of these c-jun:junD hybrids code for transactivators of AP1-containing promoters. An N-terminal segment of 79 amino acids of c-Jun converts JunD into a strong transforming protein, while other segments of c-Jun contribute to a lesser extent. Contrary to what has been reported with rat embryo fibroblasts, a c-Jun derivative with serines substituted by alanines in positions 63 and 73 still transforms CEFs efficiently.
 ...
PMID:In vitro transforming capacities of mouse c-jun:junD chimeric genes. 833 52

The effect of lipopolysaccharide (LPS) on the activation of junB in a mouse macrophage cell line (J774) was investigated. J774 cells responded to either phorbol 12-myristate 13-acetate (PMA) or LPS by the transient increase in the expression levels of c-jun and junB mRNA, but not of junD mRNA. The prior depletion of protein kinase C from J774 cells blocked the action of PMA, but not of LPS, to activate junB. Pretreatment of cells with H-89 or H-7, but not with HA1004, W-7, ML-7, or tyrphostin 47, inhibited LPS-triggered junB activation. Treatment with forskolin also activated junB of J774 cells through an H-89- or H-7-sensitive pathway. Since cAMP-dependent protein kinase activity of J774 cells was inhibited by H-89, but not by H-7, LPS appears to activate junB through a cascade involving two steps, the one sensitive to H-89 and the other to H-7. Western blot analysis showed that LPS-triggered junB activation is accompanied by the increased expression of JunB proteins in the cell lysate as well as in the nuclear extract. JunB in nuclear fraction appears to specifically bind to 12-O-tetradecanoylphorbol-13-acetate-response element (TRE), since preincubation of nuclear extracts with anti-JunB serum reduced the amount of TRE-binding proteins and since the amount of JunB, but not of c-Jun or JunD, immunoprecipitated from TRE-cross-linked nuclear proteins increased in response to LPS. Thus, JunB may play an important role in LPS-triggered gene activation.
 ...
PMID:Mechanism of lipopolysaccharide-triggered junB activation in a mouse macrophage-like cell line (J774). 839 62

Serum induces the expression of the fos and jun gene families, which encode the transcription factor AP-1. Since we previously found that activation of mast cells by IgE-antigen (Ag) induces the mRNA accumulation of c-fos, c-jun, junB and junD proto-oncogenes, we were prompted to investigate whether serum could affect such accumulation in these cells. In addition, we investigated whether serum could modulate inhibition of DNA synthesis in immunologically stimulated mast cells. Mast cells, which were cultured in the presence of fetal calf serum (FCS), were characterized by a high proliferation rate and high accumulation of the mRNA of c-fos, junB and junD proto-oncogenes. After sustained FCS deprivation both DNA synthesis and the level of c-fos mRNA were significantly decreased, as expected, whereas the level of c-jun, junB and junD mRNA were not affected. As opposed to mast cells which were cultured in the presence of FCS, immunological stimulation of FCS-deprived cells resulted in DNA synthesis inhibition and an increase in c-fos expression. The results also show that the level of c-fos mRNA was increased by either IgE-Ag or FCS up to a similar level, while these two triggers could not act synergistically to enhance this expression further. Thus, changes in DNA synthesis, induced by FCS, block the ability of the immunological challenge to inhibit mast cell growth and to enhance c-fos mRNA accumulation.
 ...
PMID:Serum modulates mast cell responses to IgE antigen stimulation. 841 82

During an acute phase response following inflammatory stimuli, specific changes occur in the synthesis and secretion of many hepatic proteins. Because the expression of differentiated function requires the coordinated regulation of many genes, we investigated the activity of general and tissue-specific transcription factors using a rat liver model of the acute phase response induced by Freund's adjuvant. Nuclear extracts and RNAs were prepared throughout a 48-h posttreatment period. Mobility shift assays revealed increased binding activity by nuclear factor-kappa B, interleukin-6 (IL-6) responsive element binding protein, and activating protein 1 (AP-1). Two AP-1 complexes were induced during the acute phase response, and correlation between their presence and transcription activity was demonstrated by transfection studies. Elevated binding activity of AP-1 also correlated with elevated levels of c-jun, junD, junB, and c-fos mRNAs. Western blots showed elevated hepatic levels of c-Jun but not c-Fos proteins during the acute phase response. In addition, IL-6, tumor necrosis factor-alpha, and IL-1 beta, cytokine regulators of the acute phase response, stimulated expression of an AP-1 responsive reporter gene introduced by DNA-mediated transfection into adult rat hepatocytes in primary culture. These findings demonstrate the complexity of AP-1 hepatic transcription factor responses to humoral regulators with direct hepatocellular effects.
 ...
PMID:Activation of activating protein 1 during hepatic acute phase response. 843 Aug 10


<< Previous 1 2 3 4 5 6 Next >>