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

The proto-oncogene c-jun encodes the major component of the transcription factor AP-1 and is thought to have important functions in cell proliferation and differentiation as well as in the cellular response to a variety of external stimuli. To investigate directly the role of c-jun in growth, differentiation and tumorigenicity we generated mouse embryonic stem (ES) cell lines in which both copies of the c-jun gene have been inactivated by homologous recombination. The disruption of both copies of the c-jun gene had no apparent effect on ES cell viability, growth rate and in vitro differentiation potential. Transcriptional activation of the c-jun, junB and c-fos genes following TPA/serum induction was unaffected and efficient transactivation of AP-1 reporter constructs was demonstrated in these cells. Remarkably, subcutaneous injection of ES cells lacking c-Jun into syngeneic mice led to a drastic reduction in the formation of teratocarcinomas. We propose that whereas most of the functions of c-Jun in ES cells appear to be complemented by other Jun proteins in vitro, functional c-Jun protein is essential for efficient tumor growth in vivo.
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PMID:Embryonic stem (ES) cells lacking functional c-jun: consequences for growth and differentiation, AP-1 activity and tumorigenicity. 128 2

The product of the c-jun proto-oncogene is the major component of the 12-O-tetradecanoyl phorbol 13-acetate (TPA)-inducible transcription factor AP-1. Jun binds to the TPA-responsive elements (TREs) present in a large number of TPA-inducible genes, thereby regulating their expression in response to activation of protein kinase C. Previously we have shown that Jun/AP-1 can also activate cAMP-responsive elements (CREs), indicating the existence of cross-talk in signal transduction at the transcriptional level. Here we show that Jun/AP-1 is activated by the cAMP-dependent protein kinase A (PKA). In transient transfection experiments, TRE activation by Jun is strongly enhanced by co-transfection of the catalytic subunit of PKA or forskolin treatment, although not in all cell types studied. Jun activity can be significantly inhibited by co-transfection of the regulatory subunit of PKA. Furthermore, we show a cell-specific increase in AP-1 binding in response to forskolin treatment. However, since direct phosphorylation of Jun by PKA does not occur, we suggest an indirect activation mechanism.
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PMID:Activation of Jun/AP-1 by protein kinase A. 133 36

Transcription factor AP-1 is constituted by the various products of the fos and jun proto-oncogene family members, which associate as dimers to bind with variable efficiency to 12-O-tetradecanoyl phorbol 13-acetate (TPA)-responsive promoter elements (TREs). We have recently shown that DNA binding of AP-1 is regulated by an inhibitory protein, IP-1, whose activity is modulated by phosphorylation. Here it is shown that although AP-1 has a very high affinity for its recognition sequence, its binding to the TRE can be quickly inhibited by the addition of IP-1. IP-1 is more active on AP-1 complexes formed during a shorter period of time. IP-1 activity is blocked by stimulation of the protein kinase C (PKC) signal transduction pathway, achieved by treating HeLa cells with phorbol esters or with a diacylglycerol analog. We observed an increase in AP-1-DNA binding after treatment of the cells with either the calcium ionophore A-23187 or dibutyryl cAMP; this could be ascribed to inhibition of IP-1 activity. A decreased IP-1 activity also correlates with the increase in AP-1-DNA binding after stimulating cells with serum. This suggests that IP-1 is an important target of the various signal transduction pathways. No effect on AP-1 and IP-1 was detected in cells transformed by Ki-ras or v-raf; nor could an effect of inhibition of protein synthesis be observed. We also analysed IP-1 regulation upon differentiation of P19 embryonal carcinoma cells by retinoic acid. We conclude that IP-1 regulation has a pivotal role in the final modulation of Fos-Jun by signal transduction pathways.
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PMID:AP-1 (Fos-Jun) regulation by IP-1: effect of signal transduction pathways and cell growth. 143 49

The proto-oncogene products c-Fos and c-Jun heterodimerize through their leucine zippers to form the AP-1 transcription factor. The transcriptional activity of the heterodimer is regulated by signal-dependent phosphorylation and dephosphorylation events. The stability of c-Fos was found to also be controlled by intracellular signal transduction. In transient expression and in vitro degradation experiments, the stability of c-Fos was decreased when the protein was dimerized with phosphorylated c-Jun. c-Jun protein isolated from phorbol ester-induced cells did not target c-Fos for degradation, which suggests that c-Fos is transiently stabilized after stimulation of cell growth. v-Fos protein, the retroviral counterpart of c-Fos, was not susceptible to degradation targeted by c-Jun.
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PMID:Targeted degradation of c-Fos, but not v-Fos, by a phosphorylation-dependent signal on c-Jun. 147 Sep 18

The ets-1 proto-oncogene codes for a transcription factor. In order to understand how ets-1 is regulated, we have cloned its promoter. We show that the promoter is inducible by serum and expression of c-Fos and c-Jun, and it is positively auto-regulated by its gene product. A 50 base-pair sequence is sufficient to confer c-Fos + c-Jun and c-Ets-1 responsiveness to a heterologous promoter. This element contains two AP1 and one Ets-1 like motifs. Striking, AP-1 and Ets-1 motifs are found in oncogene responsive units (ORU's) of other promoters, suggesting that combining these motifs is a common mechanism for generating mitogen responsive transcription elements.
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PMID:Serum, AP-1 and Ets-1 stimulate the human ets-1 promoter. 161 56

Lytic infection with herpes simplex virus (HSV) results in the repression of most host cell protein synthesis but produces an increased activity of the cellular AP-1 transcription factor. This increase is paralleled by an increase in the transcription rate of the proto-oncogene encoding the AP-1 component, c-Jun resulting in an increase in c-Jun protein in infected cells. The increased AP-1 activity in infected cells is dependent upon the HSV immediate-early protein ICPO. Thus a mutant lacking the gene encoding this protein fails to increase AP-1 activity whilst an ICPO expression plasmid can specifically increase the activity of an AP-1 dependent promoter in co-transfection experiments. The implications of these effects in the interaction of HSV with cultured cells are discussed.
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PMID:Activation of the cellular transcription factor AP-1 in herpes simplex virus infected cells is dependent on the viral immediate-early protein ICPO. 165 81

The product of the junB gene, a gene homologous to the proto-oncogene c-jun, is a component of transcription factor AP-1. JunB expression is modulated by a wide variety of extracellular stimuli, such as serum, growth factors, phorbol esters (TPA) and activators of protein kinase A (PKA). In order to study the molecular basis of this complex regulation, we have cloned the mouse junB gene from a genomic testis library, and characterized the junB promoter. Here we show that the junB promoter is activated by serum, TPA, and activated PKA. Sequences located between -91 and -44 are necessary for induction. These sequences contain a CAAT box, a G-C rich region and a previously undescribed inverted repeat (IR). The IR element can mediate induction by TPA and PKA when coupled to a heterologous promoter, and specifically binds a protein of 110 kD.
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PMID:Activation of junB by PKC and PKA signal transduction through a novel cis-acting element. 170 23

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)
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PMID:In situ hybridization analysis of c-fos and c-jun expression in the rat brain following transient forebrain ischemia. 181 28

The proto-oncogene c-jun, a major component of transcription factor AP-1, is expressed at very low levels in undifferentiated embryonal carcinoma (EC) end embryonic stem (ES) cells. Retinoic acid (RA) induced differentiation causes a strong increase in the levels of c-jun mRNA. In this paper we report the cloning and characterization of the mouse c-jun promoter. Our results show that RA treatment causes a strong enhancement in c-jun promoter activity, an effect probably mediated by the RA-receptor beta (RAR beta). Sequences located between -329 and -293 are responsible for the observed RA effect, and bind at least five different protein complexes, of which three are decreased upon RA treatment. These protein binding sites do not resemble RA-responsive elements (RARE's) found in the promoters of retinoic acid receptor beta (RAR beta) and laminin B1. Furthermore, we could not detect a direct interaction of RAR alpha and RAR beta to these sequences, indicating that RA-induced c-jun expression is an indirect effect of RAR action.
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PMID:Transcriptional control of c-jun by retinoic acid. 185 Dec 95

The AP-1 family of transcription factors, which includes the proto-oncogene products c-Jun and c-Fos, controls the stimulation of cellular genes by growth factors and the expression of oncogenes, including src and ras. Transcriptional activation by c-Jun is regulated by a cell-type-specific inhibitor that represses the activity of a transcriptional activation domain (A1) of c-Jun by operating through the adjacent negative regulatory region (delta). Here we show that cotransfection of the src or ras oncogene enhances the transcriptional activity of a GAL4:c-Jun hybrid that includes the delta-A1 region of c-Jun, suggesting that the DNA binding and dimerization domain of c-Jun is not required for stimulation by Src or Ras. Moreover, induction of c-Jun activity by Src and Ras occurs in cell lines containing the c-Jun inhibitor but not in a cell line lacking it. The region in c-Jun essential for the stimulatory action of these oncogenes maps to domain A1. These findings suggest the existence of signal-transduction pathways that result in an increase in transcriptional activity of c-Jun and AP-1 by disrupting the c-Jun:inhibitor interaction.
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PMID:v-Src and EJ Ras alleviate repression of c-Jun by a cell-specific inhibitor. 190 40


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