PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Genes, jun”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 721 records · Page 40Linked to original sources
PubMed1992

Phorbol esters stimulate the phosphorylation of c-Jun but not v-Jun: regulation by the N-terminal delta domain.

c-Jun and its oncogenic counterpart v-Jun are completely conserved within the region from Ser-63 to Ser-73; these serines are sites for phorbol ester-inducible c-Jun phosphorylation. Using a U937 human leukemic cell line stably expressing v-Jun, we have demonstrated that phorbol esters stimulate the in vivo phosphorylation of c-Jun but not v-Jun. We developed an in vitro protein kinase assay to characterize the c-Jun protein kinase and to examine the determinants underlying this differential phosphorylation. Fusion proteins between glutathione S-transferase and the N terminus of c-Jun, v-Jun, or several c-Jun mutants were used as substrates. A c-Jun kinase activity was affinity-purified 5000-fold by using glutathione S-transferase-c-Jun-glutathione-Sepharose beads and was found to phosphorylate the N terminus of c-Jun but not v-Jun or c-Jun containing a 27-amino acid N-terminal deletion found in v-Jun. These effects were also observed in vivo as phorbol 12-myristate 13-acetate did not induce the phosphorylation of v-Jun or the c-Jun deletion mutant in U937 cell lines stably expressing these proteins. These findings indicate that the delta domain of c-Jun (amino acids 34-60), which is deleted in v-Jun, plays a critical role in regulating N-terminal c-Jun phosphorylation.

Amino Acid Sequence↗
PubMed1988

Localization of the human JUN protooncogene to chromosome region 1p31-32.

The oncogene jun is the putative transforming gene of avian sarcoma virus 17; jun appears to be derived from a gene of the chicken genome and has homologues in several other vertebrate species. Recent genetic and immunological data indicate that jun codes for a protein that is closely related and probably identical to the transcription factor AP-1. We have isolated a genomic DNA clone encompassing the human cellular counterpart of the gene, JUN, and used this DNA to determine the chromosomal location of the gene. A panel of DNA preparations derived from rodent-human somatic cell hybrids with defined chromosome complements was first screened with the JUN probe. This Southern blot analysis indicated that JUN is situated on the short arm of chromosome 1. In situ hybridization then assigned JUN to chromosome region 1p31-32, a chromosomal region involved in both translocations and deletions of chromosomes seen in human malignancies.

Animals↗
PubMed1999

COP9 signalosome-directed c-Jun activation/stabilization is independent of JNK.

The basic region-leucine zipper transcription factor c-Jun regulates gene expression and cell function. It participates in the formation of homo- or heterodimeric complexes that specifically bind to DNA sequences called activating protein 1 (AP-1) sites. The stability and activity of c-Jun is regulated by phosphorylation within the N-terminal activation domain. Mitogen- and stress-activated c-Jun N-terminal kinases (JNKs) were previously the only described enzymes phosphorylating c-Jun at the N terminus in vivo. In this report we demonstrate a JNK-independent activation of c-Jun in vivo directed by the constitutive photomorphogenesis (COP9) signalosome. The overexpression of signalosome subunit 2 (Sgn2), a subunit of the COP9 signalosome, leads to de novo assembly of the complex with a partial incorporation of the overexpressed subunit. The de novo formation of COP9 signalosome parallels an increase of c-Jun protein resulting in elevated AP-1 transcriptional activity. The c-Jun activation caused by Sgn2 overexpression is independent of JNK and mitogen-activated protein kinase kinase 4. The data demonstrate the existence of a novel COP9 signalosome-directed c-Jun activation pathway.

COP9 Signalosome Complex↗
PubMed1992

Transcriptional control in hepatocytes of normal and c14CoS albino deletion mice.

The transcription rates of the albumin and alpha-fetoprotein (alpha FP) genes were reduced to marginally detectable levels in livers of newborn or fetal c14CoS albino deletion mutant mice, which lack the hepatocyte specific developmental regulation (hsdr-1) locus on chromosome 7 and die shortly after birth. However, steady-state levels of these two mRNAs in livers of mutant mice were similar to those in normal mice, where these genes are actively transcribed. In c14CoS mice, transcription rates of transcription factor genes HNF-1, C/EBP and HNF-4 were reduced, albeit to different extents. These effects are specific because transcription of the HNF-3, DBP, LAP and Jun-B genes remained normal in mutant mice. Steady-state levels of all of these mRNAs reflected the transcriptional activities. Levels of HNF-1 and HNF-4 mRNAs showed much greater depression than that of C/EBP in mutant liver. The availability of this group of transcription factors may be reduced in c14CoS hepatocytes and therefore caused depressed transcription rates of their target genes such as those encoding albumin and alpha FP. However, the normal steady-state levels of albumin and alpha FP mRNAs in mutant mice remains unexplained. Fetal c14CoS hepatocytes in primary culture did acquire competence for glucocorticoid inducible transcription of the albumin, alpha FP, HNF-4 and metallothionein genes but not of the tyrosine aminotransferase (TAT) gene. These results indicate that the hsdr-1 locus is dispensable for the glucocorticoid induced transcription of these genes but not of TAT. The effects caused by the c14CoS deletion are pleiotropic in controlling the expression of numerous genes at distinct levels in the liver.

Albinism↗
PubMed2003

Suppression of TGF-beta signaling by conophylline via upregulation of c-Jun expression.

In the course of screening for inhibitors of transforming-growth factor-beta (TGF-beta) functions we found that conophylline, a vinca alkaloid, inhibited TGF-beta-induced apoptosis in rat hepatoma cells. Because conophylline also inhibited TGF-b-induced promoter activity in mink lung cells, we studied the mechanism of the inhibition in this cell line. Conophylline did not inhibit nuclear translocation of Smad2. Instead, we found that conophylline increased the expression of c-Jun, which had been earlier shown to interact with the corepressor TGIF to suppress the transcriptional activity dependent on Smad2. Conophylline attenuated the interaction between the Smad2 complex and p300 but enhanced that between the Smad2 complex and TGIF. In cells overexpressing c-Jun, suppression of promoter activity induced by TGF-beta and the enhancement of the association of the Smad2 complex with TGIF were also observed. Thus, our data suggest that inhibition of TGF-beta-induced promoter activity by conophylline can be attributed to its potency in modulating the interaction of downstream transcriptional factors via upregulation of c-Jun expression.

Animals↗
PubMed1999

Retinoic acid repressed the expression of c-fos and c-jun and induced apoptosis in regenerating rat liver after partial hepatectomy.

Retinoic acid (RA), which was injected within 4 h after partial hepatectomy (PH), inhibited DNA synthesis in regenerating liver. The inhibition was accompanied by apoptosis, evidenced by in situ end labeling and gel electrophoresis of DNA fragmentation. Characteristic DNA fragmentation was obvious at 4 h and reached a maximum at 8 h after injection. Northern blot analysis revealed that RA repressed the expression of c-fos and c-jun at 15 and 30 min with the up-regulation of retinoic acid receptor gamma (RARgamma) and RARbeta at 2 h after PH. The transglutaminase II mRNA level and activity were increased by RA injection at 4 h and 8 h after PH, respectively. The mRNA levels of thymidylate synthase and thymidine kinase, which are rate determining enzymes of DNA synthesis, decreased in RA injected rats. No change was seen in the expression of p53 and p21WAF1/CIP1 which have been suggested to participate in the apoptosis process. These results suggest that RA exerts the antiproliferative activity only on the early stage of liver regeneration accompanied by the repression of c-fos and c-jun expression and induction of apoptosis.

Animals↗
PubMed1997

Expression of the immediate-early genes, c-fos, c-jun, and c-myc: a comparison in rats of nongenotoxic hepatocarcinogens with noncarcinogenic liver mitogens.

The involvement of the immediate-early (IE) genes c-fos, c-jun, and c-myc in regenerative liver hyperplasia is accepted, but their involvement in direct hyperplasia is uncertain. We have examined the hypothesis that the ability to induce IE genes may reflect the hepatocarcinogenic potential of a chemical. The ability of 1,4-dichlorobenzene (DCB) (300 mg/kg) (a noncarcinogenic rat liver mitogen), diethylhexyl phthalate (DEHP) (950 mg/kg), and chlorendic acid (120 mg/kg) (both nongenotoxic hepatocarcinogens) to induce c-fos, c-jun, and c-myc expression in rat liver was determined by Northern blot analysis and by in situ hybridization. Results were correlated to hepatic labeling index (LI) as determined by incorporation of BrdU in each of three lobes for each of three male F344 rats per group. Carbon tetrachloride (CCl4) (2 ml/kg) was used as a positive control. Increased LI was preceded by elevated expression of all three IE genes after CCl4, but also after DCB and DEHP, although induction by these was less marked. In all cases, there was considerable interanimal variation within groups, but little interlobe variation. Interestingly, there was a good correlation (r2 > or = 0.85) between c-myc expression and LI, but not between LI and c-fos or c-jun. Despite the disparate carcinogenic potential of DEHP and DCB, both chemicals induced similar patterns of IE gene expression, suggesting that this cannot distinguish hepatocarcinogenic liver mitogens from noncarcinogenic liver mitogens. These data assist in the evaluation of IE gene expression both as a marker of direct versus regenerative hyperplasia and as an indicator of the hepatocarcinogenic potential of liver mitogens.

Animals↗
PubMed1995

Effects of protein phosphatase inhibition by okadaic acid on the differentiation of F9 embryonal carcinoma cells.

Okadaic acid, a protein phosphatase inhibitor, is a strong tumor promoter which apparently activates protein phosphorylation. To examine the role of protein phosphatases in stem cell growth and differentiation, embryonal carcinoma F9 cells were treated with okadaic acid. In the presence of this agent, the cells showed rapid morphological changes and arrest of proliferation at the M phase of the cell cycle, accompanied by a marked increase in the mRNA expression of various differentiation markers. Okadaic acid induced rapid increase in the mRNA levels of both c-jun and junB and results indicate that the inhibition of phosphatase by okadaic acid induces apparent activation of protein phosphorylation and may cause the expression of differentiation marker genes in F9 cells via the activation of AP-1.

Animals↗
PubMed2002

Streptozotocin-induced diabetes and the neurochemistry of vagal afferent neurons.

To assess whether diabetes alters the content and/or expression of neuroactive agents and protooncogenes in afferent neurons of the vagus nerve, the nodose ganglia of streptozotocin (STZ)-induced diabetic rats were studied at 8, 16, and 24 weeks after induction of diabetes. Neuronal nitric oxide synthase (nNOS), tyrosine hydroxylase (TH), the immediate early gene c-Jun, vasoactive intestinal peptide (VIP) and calcitonin gene related peptide (CGRP) content and expression were measured in nodose ganglia of control, diabetic, and diabetic+insulin-treated rats using immunocytochemistry and reverse transcription-polymerase chain reaction (RT-PCR). The numbers of nNOS-immunoreactive (ir) neurons were increased in the nodose ganglion of diabetic compared to control rats at the 8- and 16-week time points. However, no change was noted in the nNOS mRNA content of the diabetic nodose ganglion at either time point. Moreover, no alterations in the numbers of vagal efferent NOS-containing neurons (labeled with NADPH-diaphorase histochemistry) were noted in the dorsal motor nucleus of the vagus (DMV) or the nucleus ambiguous (NA) of control, diabetic, and diabetic+insulin-treated rats at any time point. Neither the numbers of TH-ir neurons nor the content of TH mRNA was altered in the diabetic rats at the 8- and 16-week time points. However, 24 weeks of diabetes resulted in a reduction in the numbers of TH-ir neurons in the diabetic nodose ganglia when compared to control, an effect not seen in diabetic rats receiving insulin. The number of nodose ganglion neurons labeled for the protooncogene, c-Jun, was small yet slightly increased in the diabetic nodose ganglia at the 8-week time point and was reversed with insulin treatment. The increase in c-Jun-ir neurons was not found at 16 or 24 weeks of diabetes. VIP-ir and CGRP-ir were unchanged at any of the time points. These data show that diabetes affects the content of some, but not all, neuroactive agents in the nodose ganglion and may reflect a modest level of diabetes-induced damage and/or alterations in axonal transport in the vagus nerve.

Animals↗
PubMed1992

Upstream regions of the c-jun promoter regulate phorbol ester-induced transcription in U937 leukemic cells.

To understand the mechanism by which phorbol esters (PMA) stimulate c-jun transcription in human leukemic cell line U937, we have mutated specific enhancer sequences within the c-jun promoter. We find in the region of DNA from -132 to +170 containing Sp1, C-TF and AP-1 sequences that mutation of the AP-1 sequence alone is not sufficient to abrogate transcription, and mutation of the Sp1 sequence increases transcription 4-fold. Although mutation of the CTF site had no effect, CTF and AP-1 mutations together totally abrogate PMA-induced transcription. In comparison mutations of either of these sites alone or together in a construct containing -1639/+740 of the c-jun promoter had no effect on transcription. Because this data suggested the possibility of other upstream control regions, we sequenced the promoter from -142 to -1639. This sequence demonstrates a greater than 70% homology between human, and mouse c-jun promoters for the region from -142 to -441, and a second AP-1-like site in the -183 to -192 region. Mutation of this site did not influence transcription by PMA. By making constructs containing varying portions of the promoter, we have identified the region between -142 and -711 to be responsible for mediating PMA-induced c-jun transcription.

Base Sequence↗
PubMed1992

Use of antisense oligomers to study the role of c-jun in G1 progression.

In actively proliferating Swiss 3T3 fibroblasts, expression of the protooncogene c-jun is maximally induced early in G1, immediately after completion of mitosis. Within 2 hours, c-jun mRNA levels drop to a basal amount that is approximately 30% of the maximum. This is maintained throughout the remainder of G1. To access the functional implications of this pattern of c-jun expression, antisense oligomers specific to c-jun were added to either actively proliferating or synchronized Swiss 3T3 cells, and their ability to inhibit DNA synthesis and division was determined. Our results show that if Swiss 3T3 cells are treated with anti-c-jun while actively growing or at any time during G1 after completion of mitosis, they exhibit a reduced ability to enter S-phase and subsequently divide. These results demonstrate that the regulation of G1 progression following mitosis depends on the expression and function of the protooncogene c-jun.

3T3 Cells↗
PubMed2003

Efficacy validation of synthesized retinol derivatives In vitro: stability, toxicity, and activity.

Retinol (vitamin A) is used as an antiwrinkle agent in the cosmetics industry. However, its photo-instability makes it unsuitable for use in general cosmetic formulations. To improve the photo-stability of retinol, three derivatives (3, 4, and 5) were synthesized and their biological activities were analyzed. 1H NMR and HPLC analysis indicated that derivatives 3 and 5 were much more stable than retinol under our sunlight exposure conditions. When human adult fibroblasts were treated, the IC(50) of derivative 3 was 96 microM, which is similar to that of retinol, as determined by the MTT assay. Derivatives 4 and 5 were 2.5 and 8 times more toxic than retinol, respectively. At 1 microM treatment, like retinol, derivatives 3 and 4 were specifically active for RARalpha out of six retinoid receptors (RAR/RXRalpha, beta, gamma). Dose-dependent analysis confirmed that derivative 4 was as active as retinol and the other two derivatives were less active for RARalpha. The effect of our derivatives on the expression of collagenase, an indicator of wrinkle formation, was measured using the transient co-expression of c-Jun and RT-PCR in HaCaT cells. Collagenase promoter activity, which is increased by c-Jun expression, was reduced 42% by retinol treatment. The other derivatives inhibited collagenase promoter activity similarly. These results were further confirmed by RT-PCR analysis of the collagenase gene. Taken together, our results suggest that retinol derivative 3 is a promising antiwrinkle agent based on its higher photo-stability, lower RARalpha activity (possibly indicating reduced side effects), and similar effect on collagenase expression.

Adult↗
PubMed1989

Cell-specific transcriptional control of the mouse DNA-binding protein mC/EBP.

The mRNA encoding the mouse homolog of C/EBP, a rat DNA-binding protein that participates in activating a number of genes in hepatocytes, is present in liver cells at a far higher concentration than in most other cells, including spleen, kidney, muscle, and the majority of the brain. However, fat cells and intestinal cells contain 25-50% as much mRNA as liver cells. "Run-on" experiments show that the basis for the restricted cellular distribution of the mouse C/EBP mRNA is transcriptional regulation of the gene. We also show that disruption of cell-cell contacts incident to liver cell dispersion results in a prompt and extensive reduction in mouse C/EBP transcription as we had earlier shown to be the case for a group of 10 genes transcribed in a hepatocyte-specific fashion. In contrast, breaking cell contacts and plating the hepatocytes in culture leads to a prolonged increase in transcription of the Jun-B gene that encodes a widely distributed transcription factor. These results illustrate that the regulation of expression of a mammalian regulatory protein with limited tissue distribution is controlled at the level of transcription and depends on cell contacts.

Animals↗
PubMed2000

Induced expression of dominant-negative c-jun downregulates NFkappaB and AP-1 target genes and suppresses tumor phenotype in human keratinocytes.

Neoplastically transformed mouse and human keratinocytes elevate transactivation of both activator protein 1 (AP-1) and nuclear factor kappaB (NFkappaB) transcription factors. The present study addresses the question of whether elevated NFkappaB in addition to elevated AP-1-dependent gene expression is necessary for maintaining the tumor cell phenotype. When a tetracycline-regulatable dominant-negative c-jun (TAM67, having a truncated transactivation domain) was expressed in tumorigenic human keratinocytes, AP-1- and NFkappaB- but not p53-dependent reporter activity was inhibited by 40-60%. Tumor phenotype, as measured by anchorage-independent growth, was inhibited by 90%. Neither AP-1/NFkappaB activation nor expression of tumor phenotype was inhibited in TAM67-harboring keratinocytes under noninducing conditions. Electrophoretic mobility shift analysis showed that induction of TAM67 expression slightly increased AP-1- but reduced NFkappaB DNA-binding activity. Immunoprecipitation showed that TAM67 interacted in keratinocyte nuclei with NFkappaB p65, suggesting that inhibition of NFkappaB by TAM67 is mediated by direct protein-protein interactions, possibly producing decreased binding to DNA or inactivating p65. To analyze the putative effector genes that may be targeted by TAM67, expression of genes responsive to AP-1 or NFkappaB was measured by reverse transcriptase-polymerase chain reaction in TAM67 transfectants with or without TAM67 induction. Induction of TAM67 inhibited or reduced the expression of collagenase I, stromelysin I (AP-1 responsive), and interleukins 1 and 6 (NFkappaB responsive). These results indicate that genes controlled by NFkappaB and by AP-1 may be transformation-relevant targets of TAM67 and that TAM67 may inhibit NFkappaB activation through direct interaction with NFkappaB p65. Moreover, the findings provide proof for the principle of using inducible TAM67 as a gene therapy to suppress tumor phenotype in human carcinoma cells.

Cell Adhesion↗
PubMed1995

A quail long-term cell culture transformed by a chimeric jun oncogene.

A chimeric construct (VCD) consisting of parts from viral jun, chicken c-jun, and chicken junD was cloned into the replication-competent retroviral RCAS vector. This construct, RCAS-VCD, was found to have a higher focus forming potential in quail fibroblasts than the equivalent construct RCAS-VJ-1, expressing viral jun. DNAs from RCAS-VCD and RCAS-VJ-1 were transfected into primary quail embryo fibroblasts. Cells derived from one RCAS-VCD-induced focus survived cell crisis, which became manifest after 15 passages, and could be expanded into a long-term culture. This cell line, termed VCD, has been passaged for over 100 times so far. The cells grow to very high densities and then pile up into clumps of rounded cells. The culture releases a transforming virus with a titer of 10(5) FFU/ml, as tested on primary quail embryo fibroblasts. The transformed phenotype of VCD cells was verified by agar colony formation. VCD cells are capable of anchorage-independent growth with a cloning efficiency of 10%. Southern blot analysis of genomic DNA from VCD cells showed proviral integration of the RCAS construct without detectable rearrangements. Northern and Western blot analyses confirmed correct expression from integrated RCAS-VCD of predicted RNAs and of the chimeric Jun(VCD) protein. jun(VCD)-transformed cells provide a constant source of homogeneous cellular material for the investigation of the molecular mechanisms of jun-induced cell transformation and for the identification of direct and indirect targets of Jun protein function.

Animals↗