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At least 19 recordsLinked to original sources
PubMed1991

Expression of c-JUN, JUN B and JUN D proteins in rat nervous system following transection of vagus nerve and cervical sympathetic trunk.

Expression of c-JUN, JUN B and JUN D proteins was investigated in axotomized neurons following transection of the vagus nerve and the cervical sympathetic trunk in the rat. Vagotomy induced the expression of c-JUN and JUN D in the nodose ganglion, dorsal motor nucleus of the vagus nerve and nucleus ambiguus, whereas JUN B was not expressed in these areas, c-JUN and JUN D appeared after 10 h in the nodose ganglion and after 24 h in the dorsal motor nucleus of the vagus nerve with a maximum of immunoreactivity after 48 h. The c-JUN protein remained expressed at an increased level up to 100 days, whereas the immunoreactivity of JUN D declined after five days. Crush of the vagus nerve initially evoked an intense expression of c-JUN and JUN D, but in the course of regeneration the expression of c-JUN and JUN D had returned to more basal levels after 100 days. Similar to vagotomy, application of colchicine and vinblastine on to the intact vagus nerve induced expression of c-JUN and JUN D. On the other hand, application of lidocaine prior to vagotomy did not prevent the expression of these proteins. Transection of the cervical sympathetic trunk induced expression of c-JUN and JUN D, but not of JUN B, in the preganglionic sympathetic neurons of thoracic spinal cord. In these neurons, expression of c-JUN was still enhanced after 60 days whereas JUN D had returned to basal level. One hour after vagotomy, c-JUN and JUN B were transynaptically expressed in the area of central termination of sensory vagal neurons and declined within 10 h to basal levels. JUN D showed a late onset of expression, it appeared after 5 h and persisted for 60 days in this area. We postulate that the expression of c-JUN and JUN D in axotomized neurons is induced by deprivation of a target-derived suppressor.

Animals↗
PubMed1991

c-JUN, JUN B, and JUN D differ in their binding affinities to AP-1 and CRE consensus sequences: effect of FOS proteins.

We have compared the binding properties of c-JUN, JUN B, and JUN D in the absence or in the presence of c-FOS, FOS B, and FRA-1 to different AP-1 and CRE-containing oligonucleotides. The results demonstrate that for a given AP-1-containing oligonucleotide the binding affinities of the different JUN proteins are always c-JUN greater than JUN D greater than JUN B. The three JUN proteins have the capacity to bind to a CRE consensus sequence with very high affinity. We have found that c-JUN, JUN B, and JUN D bind with different affinities to different oligonucleotides containing an identical AP-1 or CRE binding site, implying that the adjacent sequences influence the stability of the JUN/DNA complexes. Interestingly, an AP-1-containing oligonucleotide which binds the JUN proteins with high affinity can be converted to a CRE-containing oligonucleotide which will also bind the different JUNs very efficiently. The heterodimers formed between the different JUN and FOS proteins have an enhanced binding activity compared to the JUN:JUN homodimers. In all cases the half-lives of the JUN:FOS/DNA complexes are longer than those of the JUN:JUN/DNA complexes. The most stable complexes were obtained in the presence of FOS B, followed by FRA-1 and c-FOS.

Animals↗
PubMed1991

Differential regulation of protooncogenes c-jun and jun D expressions by protein tyrosine kinase, protein kinase C, and cyclic-AMP mitogenic pathways in dog primary thyrocytes: TSH and cyclic-AMP induce proliferation but downregulate C-jun expression.

The expressions of the protooncogenes c-jun and jun D have been investigated in dog thyrocytes in a primary culture whose proliferation is stimulated by three distinct intracellular signaling pathways (1) the thyrotropin (TSH) or forskolin-cyclic-AMP-mediated cascade; (2) the protein kinase C pathway activated by diacylglycerol (DAG) and phorbol esters (TPA); (3) a protein tyrosine kinase system activated by epidermal growth factor (EGF). While the first cascade is compatible with the differentiated state of the cell, the two latter pathways induce dedifferentiation. Following the stimulation by TPA or EGF, the expression of c-jun was increased and the expression of jun D was faintly increased. Both expressions are superinduced in the presence of cycloheximide as in mitogenically stimulated fibroblasts but, in the presence of cycloheximide alone, the expressions of c-jun and jun D are clearly unstable with time. This indicates that cycloheximide controls should be included at all time points examined in such experiments. Increasing intracellular concentrations of cyclic-AMP by forskolin or TSH was followed by an inhibition of the expression of c-jun. This inhibition was independent of protein synthesis. Similarly, the TPA or EGF stimulation of c-jun expression was also inhibited by TSH or forskolin, as in fibroblasts in which cyclic-AMP inhibits proliferation. Our results show that the expression of c-jun is not universally correlated with the stimulation of cell proliferation. The stimulation of c-jun expression is not common between the three mitogenic pathways. It thus represents another of the very different responses elicited by the cyclic-AMP cascade as compared to the more studied tyrosine kinase and protein kinase C mitogenic pathways.

Animals↗
PubMed1991

Expression of c-jun, jun B and jun D proto-oncogenes in human peripheral-blood granulocytes.

We have found that purified human peripheral-blood granulocytes express constitutively significant levels of proto-oncogenes c-jun, jun B and jun D mRNA. Upon functional activation of granulocytes by 4 beta-phorbol 12-myristate 13-acetate (PMA), the levels of c-jun, jun B and jun D transcripts were increased. The three jun genes showed a similar time course in their induction by PMA, maximal mRNA levels being reached after 60 min of induction. These results suggest that expression of c-jun, jun B and jun D genes might be involved in terminal granulocyte differentiation or in regulating granulocyte functionality.

Blotting, Northern↗
PubMed1990

Changes in rasT24 expression do not induce changes in c-jun, jun-B, or jun-D RNA levels in rat liver epithelial cells.

We used a series of rat liver epithelial (RLE) cell lines that carry a zinc-regulatable metallothionein/rasT24 fusion gene (MTrasT24) to investigate the relation of ras oncogene expression to steady-state RNA levels of the jun family of genes. In these cells, steady-state RNA levels of c-jun, jun-B, and jun-D were unrelated to rasT24 RNA levels or the phenotypic changes induced by the ras oncogene. Steady-state levels of the three jun mRNAs varied among different rasT24 transformed clones, and, although some clones exhibited concomitant induction of rasT24 and jun mRNAs, other clones exhibited no such correlation. We conclude that the effects of rasT24 in transformed RLE cells do not appear to be mediated by c-jun, jun-B, or jun-D and that studies examining only a single transformed clone may give misleading results with respect to the role of various oncogenes in the transformation process.

Animals↗
PubMed1991

Jun B, c-jun, jun D and c-fos mRNAs in nucleus caudalis neurons: rapid selective enhancement by afferent stimulation.

In situ hybridization using cDNAs complementary to specific regions of the mRNAs encoding 3 members of the jun transcription factor gene family and c-fos reveals modest levels of hybridization over superficial laminae of the nucleus caudalis of the spinal tract of the trigeminal in sections taken from unstimulated brains. Jun B expression is markedly and rapidly enhanced ipsilateral to electrical stimulation of the trigeminal ganglion. C-fos mRNA levels also show changes, especially after higher intensity stimulation. Smaller alterations in c-jun (jun A) and jun D do not reach statistical significance. In each instance of altered expression, more neurons express hybridization densities above background levels after stimulation. Parallels between these alterations and changes in the expression of preproenkephalin in these same neuronal populations are discussed.

Afferent Pathways↗
PubMed1989

Different requirements for formation of Jun: Jun and Jun: Fos complexes.

The cFos proto-oncoprotein associates with cJun to form a heterodimer with increased DNA binding and transcriptional activities. It has been suggested that dimerization of these proteins is mediated by the interdigitation of an orderly repeat of leucine residues forming a leucine zipper. In agreement with this model, we find that binding to the AP-1 site requires dimerization of these proteins. Although cFos, itself, does not seem to dimerize and bind to the AP-1 site, Jun: Fos heterodimers have higher stability than Jun homodimers, which accounts for their increased DNA binding activity. Mutational analysis indicates that at least three of the repeated leucines of cJun are important for homodimer formation. However, these residues can be mutated without affecting formation of Jun: Fos heterodimers. In addition, several other residues present between the leucines are also important for both homo- and heterodimerization. These findings provide support for the recent proposal that these proteins dimerize via formation of a coiled coil and suggest that residues other than leucines provide specificity for this interaction. Assuming that dimerization is required for proper alignment of the DNA recognition sites, we generated a cJun mutant containing a small insertion between the dimerization and the DNA recognition domains. This mutant fails to bind DNA, but it acts as a trans-dominant inhibitor of cJun and cFos because it still dimerizes with the wild-type proteins.

Alleles↗
PubMed1992

The transcription factors c-JUN, JUN D and CREB, but not FOS and KROX-24, are differentially regulated in axotomized neurons following transection of rat sciatic nerve.

In adult rats, expression of c-JUN, JUN B, JUN D, c-FOS, FOS B, KROX-24 and CREB proteins was investigated by immunocytochemistry in L4 and L5 dorsal root ganglia and lumbar spinal cord for up to 300 days following transection of the left sciatic nerve. In dorsal root ganglia, expressions of c-JUN and JUN D were increased 10 h and 15 h after sciatic nerve transection, respectively. c-JUN was still at an elevated level after 300 days predominantly in small diameter neurons, whereas JUN D had declined to control levels after 100 days. In contrast to the JUN proteins, expression of CREB showed a delayed onset after 10 days and reached a maximum between 70 and 150 days. In motoneurons, expression of c-JUN and JUN D was increased 15 h and 25 h after sciatic nerve transection, respectively. Expression of c-JUN remained increased after 150 days, whereas JUN D had declined to control levels after 70 days. In contrast, expression of CREB declined within 30 h in axotomized motoneurons and remained on a reduced level for up to 150 days. JUN B, c-FOS, FOS B and KROX-24 were not induced either following axotomy or following a repeated nerve crush. Sciatic nerve transection including the surgical procedure transynaptically provoked a transient expression of all JUN, FOS and KROX-24 proteins in neurons of spinal dorsal horn which disappeared after 5 days except the expression of JUN D which lasted for up to 20 days. In contrast, CREB immunoreactivity was not at all altered in neurons of spinal dorsal horn. In untreated animals, CREB and to a lesser extent JUN D showed an ubiquitous expression in neurons and glia cells of spinal cord, whereas expression of c-JUN and a weak expression of FOS B were restricted to motoneurons. In neurons of the dorsal root ganglia, a basal expression was found for c-JUN, JUN D and CREB and, at a low level, for FOS B and KROX-24. c-JUN and JUN D were colocalized with CREB in many cells such as interneurons, motoneurons, dorsal root ganglion cells and glial cells indicating the possibility for both the control of c-jun and jun D expression by CREB and the competition of JUN and CREB proteins for CRE consensus sequences.

Animals↗
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↗
PubMed1989

Jun-B differs in its biological properties from, and is a negative regulator of, c-Jun.

c-Jun, Jun-B, and Jun-D proteins bind to the TPA response element (TRE) either as homodimers or as Jun-Fos heterodimers. We demonstrate that c-Jun and Jun-B nevertheless differ markedly in their ability to activate AP-1 responsive genes. c-Jun is an efficient activator of the c-jun and collagenase promoters, which contain a single TRE; Jun-B is not. Furthermore, Jun-B inhibits activation of these promoters by c-Jun. On the other hand, like c-Jun, Jun-B is an efficient activator of constructs containing multimeric TREs. Using chimeric proteins, we show that the distinct behavior of c-Jun and Jun-B is due to differences in their activation domains. Trans-activation by Jun-B depends on cooperative interactions between adjacently bound factors, while activation by c-Jun does not require such interactions. This differential behavior greatly expands the regulatory potential of the Jun family.

Animals↗
PubMed1989

jun-B inhibits and c-fos stimulates the transforming and trans-activating activities of c-jun.

We have cloned the human jun-B gene and determined its sequence and transforming and trans-activating activities. jun-B is less potent that c-jun in transforming and immortalizing primary rat embryo cells in cooperation with activated ras (effects enhanced by c-fos and TPA); unlike c-jun, jun-B does not transform Rat-1A cells alone. However, cotransfection of c-jun and jun-B into primary rat embryo cells with c-Ha-ras results in a significant decrease in transformation compared with c-jun alone, an event reversed by TPA. Cotransfection of c-jun and jun-B with or without c-fos into F9 teratocarcinoma cells results in decreased trans-activation of AP-1 compared with either gene alone. Introduction of jun-B into primary rat c-jun/ras transformants or c-jun into jun-B/ras transformants also results in a decrease in trans-activation. These findings demonstrate that, whereas jun-B and c-jun each participate in AP-1 trans-activation and malignant transformation, interactions between them involve negative regulation.

Amino Acid Sequence↗
PubMed1991

Expression of c-jun, jun-B, and c-fos proto-oncogenes in human primary melanocytes and metastatic melanomas.

Analysis of the regulation of c-jun, jun-B, and c-fos RNA transcript expression was performed in human primary melanocytes and metastatic melanoma cell strains. The medium requirements for human melanocyte in vitro growth are phorbol esters, agents that elevate intracellular cAMP levels, hormones, and growth factors. Cellular jun, jun-B, and c-fos gene expression are known to be affected by growth promoting agents. In primary melanocytes, the expression of c-jun, jun-B, and c-fos RNA transcripts was dependent on the growth-promoting agents present in the medium. Uniformly high c-jun, jun-B, and c-fos RNA transcript levels were observed in melanocytes cultivated in complete medium. Higher levels of c-jun RNA transcripts and low levels of c-fos RNA transcripts were observed in melanocytes cultivated in plain medium. In contrast, a range of c-jun, jun-B, and c-fos RNA transcript levels was detected in metastatic melanoma cell strains cultivated in medium with or without serum. In general, an increase in jun-B and c-fos RNA transcript expression and a decrease in c-jun RNA transcript expression was observed in metastatic melanomas compared to neonatal melanocytes. These data suggest a potential role for c-jun, jun-B, and c-fos genes in the transformation of melanocytes to malignant melanoma.

Blotting, Northern↗
PubMed1992

Modulation of c-jun and jun-B messenger RNA and inhibition of DNA synthesis by prostaglandin E2 in Syrian hamster embryo cells.

Fatty acid metabolites such as prostaglandins are important regulators of DNA synthesis and cell proliferation. However, the mechanisms involved in this regulation are unclear. We have examined the effects of several fatty acid metabolites on the expression of the growth-related genes c-jun and jun-B in Syrian hamster embryo cells. Treatment of cells with prostaglandin E2 (PGE2) resulted in the inhibition of epidermal growth factor (EGF)-induced DNA synthesis and c-jun mRNA accumulation, whereas PGE2 augmented EGF-stimulated jun-B mRNA and markedly stimulated jun-B accumulation in the absence of EGF. Treatment of cells with PGE2 resulted in rapid accumulation of cyclic AMP (cAMP), whereas prostaglandin F2 alpha did not stimulate cAMP formation and did not alter EGF-stimulated DNA synthesis or accumulation of c-jun or jun-B mRNA. Forskolin and 8-(4-chlorophenylthio)-cAMP mimicked the effects of PGE2 on DNA synthesis and on the expression of c-jun and jun-B, suggesting the involvement of cAMP. We have shown that EGF-induced DNA synthesis requires the formation of hydroxyoctadecadienoic acids, formed from linoleic acid by a 15-lipoxygenase, in Syrian hamster embryo cells (Glasgow et al., J. Biol. Chem., 267: 10771-10779). Inhibition of this 15-lipoxygenase blocked EGF-dependent hydroxyoctadecadienoic acid formation and mitogenesis but did not affect EGF-stimulated c-jun or jun-B mRNA accumulation. The data suggest that the modulation of EGF-dependent DNA synthesis by PGE2 is associated with altered expression of c-jun and jun-B in Syrian hamster embryo cells. In contrast, hydroxyoctadecadienoic acids appear to act downstream or divergent from c-jun and jun-B expression in the regulation of EGF-dependent DNA synthesis.

Animals↗
PubMed1989

jun-D: a third member of the jun gene family.

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.

Amino Acid Sequence↗
PubMed1992

Identification of NF-jun, a novel inducible transcription factor that regulates c-jun gene transcription.

In this study we report the identification of a novel transcription factor, termed Nuclear Factor-jun (NF-jun). This factor contributes to inducible transcription of the c-jun gene in human myeloid leukemia cells. NF-jun was, however, undetectable in nuclear proteins from human monocytes, granulocytes, resting T lymphocytes and lung fibroblasts. NF-jun shares several features with the well characterized NF-kappa B in that binding activity can be generated in cytosolic extracts by treatment with dissociating agents. In addition, binding of NF-jun to its recognition site is enhanced by treatment of cells with 12-O-tetradecanoylphorbol-13-acetate, tumor necrosis factor alpha or the protein synthesis inhibitor cycloheximide (CHX). However, as revealed by competition assays and electrophoretic mobility shift assays, purified NF-kappa B fails to bind to the c-jun fragment which contains the NF-jun site, and this fragment fails to compete with NF-kappa B for binding. UV crosslinking showed that NF-jun contains a 55 and a 125 kDa protein species. These findings demonstrate that the c-jun gene can be regulated by a transcription factor distinct from AP-1. Our findings also indicate that while NF-jun has several features in common with the NF-kappa B binding protein including its subcellular localization and its ability to translocate from the cytoplasm to the nucleus, this factor recognizes a unique DNA sequence. Moreover, the activity of this protein is differentially regulated in various cell types. NF-jun might function as a signal transducing molecule in order to mediate rapid induction of the early response gene c-jun in a cell type- and stimulus-specific manner.

Base Sequence↗
PubMed1991

Regulation of c-fos, c-jun, jun-B, and c-myc messenger ribonucleic acids by gonadotropin and growth factors in cultured pig Leydig cell.

The nuclear protooncogenes have been implicated in the coordinate regulation of gene expression during cell proliferation and differentiation. Previous work has shown that LH and human h CG as well as several growth factors including epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), transforming growth factor-beta, and insulin-like growth factor-I play a role in Leydig cell differentiated functions. To evaluate the possibility that protooncogenes mediate long term effects of these factors, their action on the levels of c-fos, c-jun, jun-B, and c-myc messenger (m) RNAs was studied. hCG (10(-9) M) produced a time-dependent increase in c-fos (9-fold), jun-B (18-fold) and c-myc (5-fold) mRNA levels but did not affect c-jun. The concentration of hCG required for half-maximal stimulation (ED50 = 7 +/- 4 x 10(-12) M) was similar to that required to induce half-maximal testosterone production. At optimal concentrations, the effects of EGF and bFGF on c-fos and jun-B mRNAs were lower than those induced by hCG, but their effects on c-myc mRNA were higher. In addition, they stimulated c-jun. Moreover, EGF and bFGF potentiated the effects of hCG on c-fos and jun-B, whereas hCG potentiated the action of growth factors on c-jun. Transforming growth factor-beta increased only jun-B mRNA, whereas insulin-like growth factor I increased c-fos, jun-B, and c-myc but less effectively than hCG. Lastly, the phorbol ester phorbol 12-myristate 13-acetate increased the level of the four protooncogene mRNAs, and its effects on c-fos and c-myc were significantly higher than those produced by hCG. These data indicate that the regulation of protooncogene mRNAs in normal Leydig cells is multifactorial. They also show differential responsiveness of the members of the Jun family to several factors. Our results are consistent with the hypothesis that the Fos and Jun families of regulatory proteins could play a role in mediating long term responses to the complex array of hormones and growth factors to which Leydig cells are exposed in vivo.

Animals↗
PubMed1992

EGF-induced jun B-expression in transfected P19 embryonal carcinoma cells expressing EGF-receptors is dependent on Jun D.

The TPA-inducible transcription factor AP-1, consisting of homo- or hetero-dimers of members of the Jun- and Fos-families, regulates transcription of a wide variety of genes containing the TPA response element (TRE). In P19 embryonal carcinoma (EC) cells, Jun D is the only component of AP-1 expressed, while in these cells until now none of the members of the jun- and fos-families have been found to be inducable by external stimuli. Here we demonstrate that Jun B is the only member of the Jun- and Fos-families that is induced by Epidermal Growth Factor (EGF) in transfected murine P19 EC cells, expressing functional human EGF receptors (hEGF-Rs). Induction of jun B can be mimicked in wild type P19 EC cells by the synergistic action of the phorbol ester TPA and the calcium ionophore A23187, through activation of signal transduction pathways, that are activated simultaneously by EGF. The EGF induced jun B expression in the hEGF-R expressing P19 EC cells is mediated by an inverted repeat (IR) sequence in the jun B promoter, previously shown to be responsive to both PKC and PKA signal transduction. Transactivation of the IR sequence by EGF can be blocked completely by prior expression of antisense Jun D, but not by antisense c-Jun. These studies therefore implicate Jun D in the regulation of immediate early gene expression by external stimuli.

Blotting, Northern↗
PubMed1992

Regulation of c-jun and jun-B by progestins in T-47D human breast cancer cells.

To investigate further the molecular mechanisms of progestin regulation of human breast cancer cell growth, we studied the effect of progestins on expression of the protooncogene c-jun and other members of the jun family, jun-B and jun-D, in T-47D human breast cancer cells. The progestin medroxyprogesterone acetate (MPA) increased c-jun mRNA levels in a time- and dose-dependent fashion. Maximal effects were seen after 3 h of treatment with 10-100 nM MPA. Under these conditions, the c-jun mRNA was increased 5.4-fold above the control level. Although the c-jun mRNA level was increased by cycloheximide alone, a further 2.4-fold increase was seen when the cells were treated with MPA in the presence of cycloheximide. The p39 c-jun protein was also increased 3.8-fold by this treatment. Maximum levels of p39 c-jun protein were achieved 9 h after treatment, and this level was maintained for at least 24 h. Dexamethasone and dihydrotestosterone did not increase the p39 c-jun protein level under these conditions. However, MPA treatment of T-47D cells resulted in a 55% decrease in overall AP-1 activity, as measured by transient transfection of an AP-1-regulated chloramphenicol acetyltransferase reporter gene. These effects were all reversible by cotreatment with a 10-fold higher concentration of the antiprogestin RU 486. MPA decreased jun-B mRNA levels 50% 1 h after treatment in T-47D cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Northern↗