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

Induction of mouse glutathione S-transferase (GST) Ya gene expression by a variety of chemical agents is mediated by a regulatory element, EpRE, composed of an Ets and two adjacent AP-1-like binding sites. In this report we present evidence that the basal and inducible activity of EpRE is mediated by AP-1 transcription factor and that the cooperative interaction between AP-1 and an Ets protein contributes to enhance the EpRE inducibility. We also show that EpRE, similar to a single AP-1 site, when ligated to GST Ya gene promoter, is transactivated by c-Fos/c-Jun or c-Fos/Jun-B heterodimer and that c-Jun/c-Jun homodimer is an activator of an AP-1 site only in the context of collagenase gene promoter.
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PMID:Cooperative interaction between Ets and AP-1 transcription factors regulates induction of glutathione S-transferase Ya gene expression. 816 97

Interactions between the glucocorticoid receptor (GR) and c-Jun/c-Jun homodimer (JUN) on the promoter DNA of mouse mammary tumor virus-long terminal repeat (MMTV-LTR) are reported here using the electrophoretic mobility shift assay (EMSA). Both GR and JUN are capable of independently binding to their respective response elements, including glucocorticoid response element (GRE) and phorbol ester response element (TRE), on MMTV-LTR promoter. The protein-DNA complex, assembled by pre-incubating JUN and DNA before the addition of GR, migrates slower (supershift) on gel electrophoresis than do the complexes formed by the other orders of addition. The formation of the supershifted complex is GR and JUN dose-dependent. The supershift is not detected with the cleaved fragments of MMTV-LTR promoter that separate GRE from TRE, indicating that the integrity of the promoter and possibly the spacing between GRE and TRE are important. The interaction of GR and JUN on the MMTV-LTR promoter appears to be more complex than simple protein-protein interaction.
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PMID:Assembly of glucocorticoid receptor and c-JUN homodimer on the promoter of mouse mammary tumor virus-long terminal repeat is influenced by order of addition. 828 Jan 42

CRE-BPa, here designated as CRE-BPa alpha, is a novel member of the CRE (cAMP response element)-binding protein CRE-BP1 family. CRE-BPa alpha has four regions highly homologous to CRE-BP1, including a putative metal finger structure and a DNA-binding domain consisting of a basic amino acid cluster and a leucine zipper. CRE-BPa specifically binds to CRE as a homodimer or heterodimer with c-Jun or CRE-BP1. Here we report three alternative splicing forms of CRE-BPa alpha: two of them, CRE-BPa beta and CRE-BPa gamma, lack the N-terminal 7 and 33 amino acids of CRE-BPa alpha, and the third one CRE-BPa delta, has 16 additional amino acids in the N-terminus and amino acids 156-508 of CRE-BPa alpha. In CAT cotransfection experiments using CV-1 cells, transient expression of each of four CRE-BPa proteins caused a 1.6- to 3.4-fold increase of CRE-dependent transcription, respectively. Interestingly, these weak trans-activating capacities of CRE-BPa proteins were enhanced 2.7- to 3.6-fold by treatment of cells with 12-O-tetradecanoyl-phorbol 13-acetate (TPA). However, CRE-BPa did not affect the TPA-induced and TRE (TPA response element)-dependent transcription. These results indicate that CRE-BPa is a CRE-dependent trans-activator, and that CRE-BPa can confer TPA inducibility on CRE. Thus, CRE-BPa has an unique characteristic of cross-talk between cAMP pathway and TPA pathway.
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PMID:Regulation of trans-activating capacity of CRE-BPa by phorbol ester tumor promoter TPA. 837 84

Among multiple CRE (cyclic AMP response element)-binding proteins, CRE-BP1 (also designated ATF-2) has two unique characteristics: it mediates the adenovirus E1A-induced trans-activation and forms a heterodimer with c-Jun. Two structures, a putative metal finger and a leucine zipper, in CRE-BP1 are responsible for these capacities. As a new member of a CRE-BP1 family that has similar metal finger and leucine zipper structures, we have isolated cDNA clones of CRE-BPa by cross-hybridization with CRE-BP1 cDNA. CRE-BPa protein consists of 508 amino acids and has a molecular weight of 56,840. CRE-BPa protein is highly homologous with CRE-BP1 in four regions: two of them are the regions containing the putative metal finger or the DNA-binding domain consisting of the basic amino acid cluster and the leucine zipper. Like CRE-BP1, CRE-BPa binds to CRE with higher affinity than to the 12-O-tetradecanoylphorbol-13-acetate response element as a homodimer or a CRE-BPa/c-Jun or CRE-BPa/CRE-BP1 heterodimer. However, using the c-Myb-CRE-BPa fusion protein, it was show that CRE-BPa could not mediate the E1A-induced trans-activation. Expression of CRE-BPa mRNA was found in a limited number of cell lines, and multiple sizes of CRE-BPa mRNA species were detected in some cell lines and tissues. CRE-BPa will be useful to clarify the mechanism of CRE-mediated transcriptional activation by E1A or c-Jun.
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PMID:Isolation and characterization of a novel member of the gene family encoding the cAMP response element-binding protein CRE-BP1. 844 Jul 10

The transcription factor c-Fos is a short-lived cellular protein. The levels of the protein fluctuate significantly and abruptly during changing pathophysiological conditions. Thus, it is clear that degradation of the protein plays an important role in its tightly regulated activity. We examined the involvement of the ubiquitin pathway in c-Fos breakdown. Using a mutant cell line, ts20, that harbors a thermolabile ubiquitin-activating enzyme, E1, we demonstrate that impaired function of the ubiquitin system stabilizes c-Fos in vivo. In vitro, we reconstituted a cell-free system and demonstrated that the protein is multiply ubiquitinated. The adducts serve as essential intermediates for degradation by the 26S proteasome. We show that both conjugation and degradation are significantly stimulated by c-Jun, with which c-Fos forms the active heterodimeric transcriptional activator AP-1. Analysis of the enzymatic cascade involved in the conjugation process reveals that the ubiquitin-carrier protein E2-F1 and its human homolog UbcH5, which target the tumor suppressor p53 for degradation, are also involved in c-Fos recognition. The E2 enzyme acts along with a novel species of ubiquitin-protein ligase, E3. This enzyme is distinct from other known E3s, including E3 alpha/UBR1, E3 beta, and E6-AP. We have purified the novel enzyme approximately 350-fold and demonstrated that it is a homodimer with an apparent molecular mass of approximately 280 kDa. It contains a sulfhydryl group that is essential for its activity, presumably for anchoring activated ubiquitin as an intermediate thioester prior to its transfer to the substrate. Taken together, our in vivo and in vitro studies strongly suggest that c-Fos is degraded in the cell by the ubiquitin-proteasome proteolytic pathway in a process that requires a novel recognition enzyme.
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PMID:Degradation of the proto-oncogene product c-Fos by the ubiquitin proteolytic system in vivo and in vitro: identification and characterization of the conjugating enzymes. 852 78

Apoptotic cell death was induced in rat thymocytes on exposure to calcium ionophore A 23187 (100 micron(s)) for 24 h as observed from morphological changes and DNA fragmentation into oligonucleosomal ladder. The cell death was independent of de novo syntheses of protein. However, the involvement of c-Myc, c-Jun, poly ADPR polymerase and antioxidant enzymes CuZn SOD and catalase was observed.
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PMID:Calcium ionophore A 23187 induces apoptotic cell death in rat thymocytes. 891 72

Experiments were designed to clarify the role of c-Jun/c-Fos and of putative phorbol 12-myristate-13-acetate-(PMA)-responsive elements (TREs) in the induction of plasminogen-activator inhibitor 1 (PAI-1) gene transcription in the human hepatoma cell line HepG2 by activators of protein kinase C (PKC). Treatment of HepG2 cells with the phorbol ester PMA or serum rapidly and transiently increased c-Jun and c-Fos mRNA and protein levels prior to PAI-1 induction. This induction of PAI-1 gene transcription was found to be dependent on ongoing protein synthesis. An essential role of c-Jun and c-Fos in basal and PMA-stimulated transcription of the PAI-1 gene is demonstrated by our finding that antisense c-jun and c-fos oligodeoxynucleotides both strongly reduced basal and PMA-stimulated PAI-1 synthesis. Since it has already been shown that two TREs between positions -58 and -50 and between -79 and -72 of the PAI-1 promoter are essential for basal and PMA-induced PAI-1 promoter activity ([16]), we examined binding of nuclear proteins to these elements. The protein-binding activity to the TRE between positions -79 and -72 shows very strong PMA induction of an unknown factor, which is not related to c-Jun or c-Fos. The TRE binding between positions -58 and -50 forms two complexes, both containing c-Jun protein. The faster migrating complex primarily contains c-Jun homodimers. The amount of the faster migrating complex is enhanced more than 30-fold in PMA-treated cells, due to a strongly increased binding of c-Jun homodimers and, to a minor extent, to binding of c-Jun/c-Fos heterodimers. Dissociation experiments suggest that the c-Jun/c-Fos heterodimers bind with much lower affinity compared to binding of c-Jun homodimers. Together with the finding that both antisense c-jun and antisense c-fos oligodeoxynucleotides reduced the amount of c-Jun homodimer, we conclude that binding of c-Jun homodimer to the TRE at positions -58 to -50 is important in the basal activity and PMA activation of the PAI-1 promoter in HepG2 cells.
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PMID:Role of c-Jun and proximal phorbol 12-myristate-13-acetate-(PMA)-responsive elements in the regulation of basal and PMA-stimulated plasminogen-activator inhibitor-1 gene expression in HepG2. 891 35

Recent studies have indicated that ubiquitously expressed molecular chaperones of the heat shock protein (Hsp) class may have an additional, nuclear, role in the regulation of gene expression. Experiments on cellular transcription factors derived from the rat adrenal gland have now shown that Hsps modulate in vitro DNA binding activity of the AP-1 factor. Both Hsc70 (p73) and Hsp70 (p72) were demonstrated to exert this effect through a mechanism that appears to be independent of both redox, and phosphorylation state. Further studies on the effect of Hsps on recombinant Fos/Jun protein binding activity indicated that the mechanism of action involves a selective attenuation of high affinity c-Fos:c-Jun binding as compared with c-Jun homodimer binding activity. Because cellular and physiological stress are associated with the induction of both AP-1 and Hsps it is apparent that Hsps may play a modulatory role in the regulation of AP-1 responsive genes.
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PMID:Modulation of cellular AP-1 DNA binding activity by heat shock proteins. 936 38

The alpha chain of the nascent polypeptide-associated complex (alpha-NAC) coactivator was shown to potentiate the activity of the homodimeric c-Jun activator, while transcription mediated by the c-Fos/c-Jun heterodimer was unaffected. The use of deletion mutants in pull-down assays revealed that alpha-NAC interacted with amino acids 1 to 89 of the c-Jun protein and that the coactivator could interact with both the unphosphorylated and the serine 73-phosphorylated form of c-Jun. N-terminal-deleted c-Jun protein failed to interact with alpha-NAC in mammalian two-hybrid assays, while mutant c-Jun proteins lacking the leucine zipper or the basic domain retained interaction with alpha-NAC in vivo. Kinetics studies with purified c-Jun homodimer and recombinant alpha-NAC proteins allowed determination of the mechanism of coactivation by alpha-NAC: the coactivator stabilized the AP-1 complex formed by the c-Jun homodimer on its DNA recognition sequence through an eightfold reduction in the dissociation constant (kd) of the complex. This effect of alpha-NAC was specific, because alpha-NAC could not stabilize the interactions of JunB or Sp1 with their cognate binding sites. Interestingly, the expression of alpha-NAC was first detected at 14.5 to 15 days postconception, concomitantly with the onset of ossification during embryogenesis. The alpha-NAC protein was specifically expressed in differentiated osteoblasts at the centers of ossification. Thus, the alpha-NAC gene product exhibits the properties of a developmentally regulated, bone-specific transcriptional coactivator.
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PMID:Bone-specific expression of the alpha chain of the nascent polypeptide-associated complex, a coactivator potentiating c-Jun-mediated transcription. 948 46

Physiological and therapeutic activities of glucocorticoids and other steroid hormones are mediated by the family of steroid hormone receptors. In addition to the classical mode of receptor action which involves binding as a dimer to regulatory sequences in target gene promoters and subsequent activation of transcription, a second mode of action is based predominantly on protein-protein interactions. As the paradigm of this so-called transcriptional cross-talk, the glucocorticoid receptor (GR) and the AP-1 transcription factor interact on target gene promoters which contain only a binding site for either one of the two transcription factors. Most frequently negative interference of both factors with each other's activity has been observed, for example, when AP-1 is composed of c-Fos and c-Jun; however, synergism is also possible under cell-specific conditions and when AP-1 is a homodimer of c-Jun. Since the detection of the GR/AP-1 cross-talk numerous other examples of transcription factor interactions have been described. Many members of the nuclear hormone receptor superfamily, including class II receptors, have been shown to participate in such cross-talk. Moreover, the transcription factor families of NF-kappaB/Rel as well as Stat, Oct, and C/EBP are engaged in cross-talk with steroid receptors. Despite the identification of a multitude of target genes which appear to be regulated by this type of transcription factor interaction, the exact molecular mechanism of the cross-talk has not yet been elucidated. This review discusses the current models to explain the molecular events of transcription factor cross-talk. Concepts are emphasized which suggest that the classical and the cross-talk mode of steroid receptor action can be triggered separately by the choice of specific ligands. A final section summarizes the partially contradictory data which assign a certain type of receptor action to a biological response particularly in the immune system.
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PMID:Transcriptional cross-talk, the second mode of steroid hormone receptor action. 966 Jan 62


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