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

The coding sequences of murine c-jun, junB, or junD, which code for proteins with practically identical dimerization and DNA binding properties, were introduced into a nondefective retroviral vector, and the phenotype of primary avian fibroblasts chronically infected with each of these viruses was studied. Cells expressing c-jun grew in low-serum medium and developed into colonies in agar, two properties characteristic of in vitro transformation. Cells expressing junB grew in agar, with a reduced efficiency as compared to c-jun, but did not grow in low-serum medium. Finally, no effect of junD expression on cell growth was observed. These different phenotypes suggest that these three closely related transcription factors play distinct roles during normal cell growth. Analysis of c-jun deletion mutants and of c-jun/junB and c-jun/junD chimeric genes showed that the N-terminal portion (amino acids 2-168) of the c-Jun protein that is involved in transcriptional activation is required for efficient transformation. On the contrary, cells expressing a truncated mouse c-Jun lacking this N-terminal domain grew slower than normal embryo fibroblasts. The reduced growth rate may be related to the finding that expression of the intact or the truncated mouse c-jun repressed the endogenous avian c-Jun homologue, suggesting that functional c-Jun product is required for normal cell growth.
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PMID:Overexpression of c-jun, junB, or junD affects cell growth differently. 192 49

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.
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PMID:Elevation of AP1 activity during F9 cell differentiation is due to increased c-jun transcription. 196 81

Mutational analyses of Jun show that the leucine zipper mediates dimerization with other Jun molecules or with the Fos protein and determines the three-dimensional orientation of the adjacent basic region, facilitating interaction with DNA. The basic region of Jun is the DNA contact surface. Substitution of certain basic residues in this region leads to loss of DNA binding. Some basic region mutants also act as transdominant lethals: they are able to tie up wild type protein in inactive complexes. The definition of transactivator domains with deletion mutants of Jun appears to depend on the assay for transcriptional activation. CAT assays suggest multiple transactivator regions in the N-terminal third of Jun, while in vitro transcription assays detect a negative regulator of transcription in this region. Another transactivator domain appears to be located close to the basic region in both c-Jun and JunD. The genetics of Jun supports a hierarchical order of Jun functions in which dimerization is a prerequisite for both DNA binding and transcriptional activation, and DNA binding is needed for transcriptional activation.
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PMID:The genetics of jun. 213 8

Introduction of the zta gene of Epstein-Barr virus into latently infected B cells leads to induction of the entire lytic cycle program of the virus. The Zta gene product is a sequence-specific DNA-binding protein of 35 kilodaltons that behaves as a specific transcriptional transactivator in transient cotransfection assays. All known Zta-responsive target promoters contain one or more members of a family of consensus-binding sites known as ZREs. On the basis of the presence of limited amino acid similarity within a basic carboxy-terminal domain, Zta has been proposed to be a highly divergent member of the c-Jun/c-Fos/GCN4 family of AP-1-binding proteins. We show here that in vitro-translated Zta and the Jun:Fos proteins have overlapping but distinct target DNA-binding specificies; both recognize canonical AP-1 sites, but only Zta recognizes ZRE sites and only Jun:Fos recognizes CRE sites. The relative binding affinity of Zta for oligonucleotides containing the 7-base-pair c-Fos AP-1 site TGAGTCA was twofold greater than that for the ZRE core motifs TGAGCAA, TG TGCAA, and TGAGTAA, but 10-fold greater than that for TGTGTCA, as measured by gel mobility retardation and competition DNA-binding assays. Cross-linking and cotranslational heterodimerization assays showed that like GCN4, Zta forms a stable homodimer in both its DNA-bound and unbound forms. Furthermore, we show that a potential coiled-coil helical domain adjacent to the basic domain of Zta can substitute for the leucine zipper of c-Fos to produce a DNA-binding protein that has a very stringent target DNA specificity and can only recognize symmetric 9-base-pair AP-1 sites (ATGAGTCAT). Therefore, despite the absence of the repeated heptad leucine zipper motifs, the Zta protein retains the characteristic features of a juxtaposed basic region and an exactly aligned coiled-coil alpha-helical dimerization domain of the bZIP class of transcriptional regulatory factors.
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PMID:The Epstein-Barr virus Zta transactivator: a member of the bZIP family with unique DNA-binding specificity and a dimerization domain that lacks the characteristic heptad leucine zipper motif. 216 45

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.
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PMID:Characterization of junD: a new member of the jun proto-oncogene family. 250 80

Treatment of adenovirus-infected mouse S49 cells with cAMP analogs leads to the transcriptional induction of early viral genes. E1A proteins and cAMP work in synergy to activate several of these genes. We now demonstrate that the transcription factor AP-1 is modestly induced by cAMP in S49 cells and induced to significantly higher levels by cAMP in the presence of E1A proteins. Cytoplasmic levels of c-fos and junB mRNAs are rapidly increased by cAMP, and the induction is substantially stronger in the presence of E1A protein. The AP-1 activity binds efficiently to both AP-1 and activating transcription factor (ATF)/cAMP response element binding protein (CREB)-binding sites present in E1A-inducible promoters and presumably plays a role in the transcriptional activation of adenovirus genes by E1A proteins and cAMP.
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PMID:Induction of transcription factor AP-1 by adenovirus E1A protein and cAMP. 255 73

The hepatitis B virus (HBV) X protein (pX) is capable of activating transcription regulated by viral and cellular promoters containing binding sites for different transcription factors, including AP1. In this study we have analyzed the mechanisms of AP1 induction by pX. The hepatitis B virus transactivator was able to activate TRE (12-O-tetradecanoylphorbol-13-acetate response element)-directed transcription in different cell lines, including HepG2, HeLa, CV1, and PLC/PRF/5 cells. pX-induced AP1 activation in HepG2 cells was associated with an increase in the DNA-binding activity of c-Jun/c-Fos heterodimers, which was not dependent either on an increase in the overall amount of c-Fos and c-Jun proteins in the cells or on formation of dimers between pX and the two proteins, thus suggesting the involvement of posttranslational modifications of the transcription factor. The observation that the overexpression of c-Jun and c-Fos in the cells results in a strong augmentation of the effect of pX on TRE-directed transcription is additional evidence indicating the involvement of posttranscriptional modifications of c-Jun/c-Fos heterodimers. The increased AP1 binding observed in the presence of pX was unaffected by the protein kinase C inhibitors calphostin C and sphingosine and by the protein kinase A inhibitor HA1004, while it was almost completely blocked by staurosporine, a potent and nonspecific protein kinase inhibitor, suggesting that protein kinase C- and A-independent phosphorylation events might play a role in the phenomenon. The ability of pX also to increase TRE-directed transcription in cell lines in which AP1-binding activity is not increased (i.e., HeLa, CV1, and PLC/PRF/5 cells) suggests that pX can activate canonical TRE sites by different mechanisms as well.
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PMID:Induction of the DNA-binding activity of c-jun/c-fos heterodimers by the hepatitis B virus transactivator pX. 750 9

The 86-kDa immediate-early 2 protein (IE2 86) of human cytomegalovirus is a powerful transactivator of homologous and heterologous promoters, including the human cytomegalovirus 1.2-kb RNA early promoter. Two potential mechanisms for gene activation by IE2 86 include interaction with cellular proteins and direct DNA binding. In this report, we show that the 1.2-kb RNA promoter contains a cis-acting AP-1 site, critical for its activation by IE2 86 in vivo, and that IE2 86, purified as a glutathione S-transferase-IE86 fusion protein, can interact with c-Jun and JunB. Additionally, by coimmunoprecipitation, we document that JunB and IE2 86 do associate in vivo. Further in vitro analysis reveals that Fos proteins are able to associate with glutathione S-transferase-IE86 only when present as a Jun-Fos heterodimer. With a set of IE2 86 mutants, we demonstrate that three independent regions of the IE2 86 interact in vitro with c-Jun, two of which are essential for activation of the 1.2-kb RNA promoter in vivo. We also show that IE2 86 can bind directly to this promoter through a sequence located just upstream of the AP-1 site between nucleotides -125 and -97. This discrete domain shares sequence homology with the cis-repression signal on the IE gene.
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PMID:The human cytomegalovirus IE2 86-kilodalton protein interacts with an early gene promoter via site-specific DNA binding and protein-protein associations. 766 55

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.
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PMID:Increased expression of c-jun, junB, AP-1, and preproenkephalin mRNA in rat striatum following a single injection of caffeine. 775 31

Induction of phase 2 detoxification enzymes by phenolic antioxidants can account for prevention of tumor initiation but cannot explain why these compounds inhibit tumor promotion. Phase 2 genes are induced through an antioxidant response element (ARE). Although the ARE resembles an AP-1 binding site, we show that the major ARE binding and activating protein is not AP-1. Interestingly, AP-1 DNA binding activity was induced by the phenolic antioxidant tert-butylhydroquinone (BHQ), but the induction of AP-1 transcriptional activity by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) was inhibited by this compound. BHQ induced expression of c-jun, junB, fra-1, and fra-2, which encode AP-1 components, but was a poor inducer of c-fos and had no effect on fosB. Like c-Fos and FosB, the Fra proteins heterodimerize with Jun proteins to form stable AP-1 complexes. However, Fra-containing AP-1 complexes have low transactivation potential. Furthermore, Fra-1 repressed AP-1 activity induced by either TPA or expression of c-Jun and c-Fos. We therefore conclude that inhibitory AP-1 complexes composed of Jun-Fra heterodimers, induced by BHQ, antagonize the transcriptional effects of the tumor promoter TPA, which are mediated by Jun-Fos heterodimers. Since AP-1 is an important mediator of tumor promoter action, these findings may explain the anti-tumor-promoting activity of phenolic antioxidants.
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PMID:Antitumor promotion by phenolic antioxidants: inhibition of AP-1 activity through induction of Fra expression. 776 34


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