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

We have recently observed that protein kinase C (PKC) was involved in the regulation of the accumulation of mRNAs of the AP-1 components in cultured Abelson-transformed murine fetal-liver-derived mast cells stimulated by exocytotic stimuli. Here we analyzed the probable regulatory effect of PKC on the synthesis and DNA-binding activity of AP-1 complexes in immunologic stimulated mast cells. In this study we used the interleukin-3--dependent murine fetal-liver--derived mast cells that were not transformed by the Abelson oncogene. Study of PKC-depleted cells showed PKC dependency of c-fos mRNA accumulation and protein expression in IgE-Ag stimulated cells. In contrast, the c-jun mRNA accumulation was unaffected by PKC depletion, whereas its protein expression was dependent on this enzymatic activity. This suggests the involvement of PKC in the regulation of translation of c-Jun, a level of c-Jun regulation that was not previously described. The amount of AP-1 DNA-bound complex was also lowered in PKC-depleted cells. Therefore, PKC plays an important regulatory role in different stages of the signal transduction pathway because of IgE-Ag stimulation. Surprisingly, we have observed that although the amount of total synthesized c-Fos began to increase 15 minutes after immunologic stimulation, the amount of c-Fos associated with Juns did not increase, even after 45 minutes. This association was not affected by PKC. Using a Fos-interacting protein (FIP)-cDNA probe, an expression of 2.9 kb mRNA was detected in these cells. Furthermore, immunologic stimulation caused an increase in the amount of a Fos-containing protein complex that bound to an FIP-binding DNA oligonucleotide. Therefore, we propose that this protein complex that contains most of the immunologically induced c-Fos has an important role in IgE-Ag-stimulated signal transduction.
 ...
PMID:Regulation of AP-1 expression and activity in antigen-stimulated mast cells: the role played by protein kinase C and the possible involvement of Fos interacting protein. 826 Jul 11

Colonization or emergence of microbial pathogens may result in tissue destruction by activation of one or more of five distinct host degradative pathways (matrix metalloproteinase pathway, plasminogen-dependent pathway, phagocytic pathway, PMN-serine proteinase pathway and osteoclastic bone resorption) or by direct cleavage of extracellular matrix constituents by microbial proteinases. Activation of endogenous destructive pathways may be mediated by immune responses resulting in expression of degradative cellular phenotypes among both immigrant and resident cell populations. In addition, expression of degradative phenotypes may be triggered by direct influences on host cells of microbial products (LPS, enzymes, toxins). A body of evidence suggests that each of these mechanisms involves local production of proinflammatory cytokines and growth factors. The matrix metalloproteinase pathway is centrally involved in dissolution of all unmineralized connective tissues and perhaps in resorption of bone as well. The matrix metalloproteinase family consists of nine or more genetically distinct Zn++ endopeptidases which collectively cleave all of the constituents of the extracellular matrix. Recent studies have uncovered many essential elements of a complex, but still incomplete, regulatory network that governs tissue destruction. Proinflammatory cytokines and growth factors induce signalling pathways several of which are dependent on protein kinase C and result in transient expression of the transcription factors c-jun and c-fos. Initiation of transcription of most matrix metalloproteinase genes requires binding of the transcription factor AP-1 (c-jun/c-fos) to a specific promoter sequence but attainment of maximal transcription rates is dependent on interaction with other promoter elements as well. Several matrix metalloproteinases have been detected in crevicular fluids and tissues of inflamed human gingiva as have the proinflammatory cytokines (IL-1 and TNF-alpha) which regulate their transcription. Although the mere presence of enzymes and cytokines does not necessarily impart function per se, these observations suggest that some level of spatial or temporal linkage exists between metalloproteinase/cytokine expression and gingival inflammation.
 ...
PMID:Role of cytokines and inflammatory mediators in tissue destruction. 826 20

Integrated hepatitis B virus DNA cloned from hepatitis B virus-associated hepatocellular carcinoma frequently contains 3'-truncated middle surface genes (preS2/St), which were recently found to have a transcriptional transactivator function. Because preS2/St, among others, is able to transactivate the promoters of the cellular oncogenes c-myc and c-fos, it has been speculated that integrated preS2/St genes might contribute to hepatitis B virus-associated liver carcinogenesis. In this study, we investigated the mechanism of target gene stimulation by preS2/St. It was found that deletion of a fragment containing the binding site for transcription factor AP-1 (Jun-Fos) substantially decreases inducibility of the human c-myc promoter by preS2/St. A subsequent investigation of AP-1 activation by preS2/St revealed the following: (a) insertion of multimeric AP-1 binding sites confers inducibility to an otherwise unstimulatable test promoter; (b) transactivation of AP-1 sites is dramatically increased when Jun and Fos are overexpressed by cotransfected expression plasmids; and (c) inhibitors of AP-1 activation also impair transactivation by preS2/St. Besides AP-1, preS2/St was also able to utilize the unrelated transcription factors NF-kappa B and AP-2 for transactivation, suggesting that the gene product of preS2/St acts indirectly through one or several general cellular pathways rather than as a bona fide transcription factor. Because AP-1 conveys induction of a large panel of tumor-relevant genes, its preS2/St-dependent activation implies a possible causative role in hepatitis B virus-associated hepatocarcinogenesis.
 ...
PMID:The hepatitis B virus preS2/St transactivator utilizes AP-1 and other transcription factors for transactivation. 827 60

The involvement of the nuclear protooncogenes c-fos and c-jun in the immediate early response of pig dermis cells was studied after in vivo gamma-irradiation. Following high radiation doses (8 to 48 Gy), the two protooncogenes were concomitantly induced, although c-fos induction was preferential. Both inductions were time and dose dependent. Therefore, the early response of the skin to high doses of radiation might involve heterodimeric activator protein 1 composed of c-Fos and c-Jun proteins. Following low radiation doses (0.5 to 2 Gy), c-jun was not induced. By contrast, dramatic c-fos induction was observed after 0.5 Gy, suggesting a specific role for c-fos at low doses.
 ...
PMID:Preferential induction of c-fos versus c-jun protooncogene during the immediate early response of pig skin to gamma-rays. 832 35

Urokinase-type plasminogen activator (uPA) is an extracellular protease and expressed in various cells that exhibit dynamic changes in cell morphology, suggesting a link between cytoskeletal reorganization (CSR) and uPA expression. CSR can be induced by pharmacological agents, such as by colchicine for microtubule cytoskeleton and by cytochalasin for microfilament cytoskeleton. Using these agents, we previously showed that CSR induced the uPA gene in LLC-PK1 cells independently of the protein kinase C and cAMP-dependent protein kinase. Here we show that the induction of the uPA gene by CSR is mediated by the activation of c-Jun which interacts with an AP-1-like site located 2 kb upstream of the uPA gene. 12-O-tetradecanoylphorbol 13-acetate (TPA) induces the uPA gene through the same elements, but additionally utilizes an adjacent PEA3 element and induces c-fos. Furthermore, CSR induces a greater accumulation and a more pronounced phosphorylation of c-Jun than TPA induction. AP-1 is a positive regulator of growth and oncogenesis, and CSR is an integral part of these processes. Our results provide a view how CSR and AP-1 could be coupled in these processes. We also show that TPA and CSR act synergistically, suggesting a model where an initial activation signal could be amplified by CSR.
 ...
PMID:Cytoskeletal reorganization and TPA differently modify AP-1 to induce the urokinase-type plasminogen activator gene in LLC-PK1 cells. 834 15

The c-fos and c-jun proto-oncogenes encode components of the transcription factor AP-1. To determine whether transformation by the v-fos or v-jun oncogene results in alterations in the level or regulation of this factor, we have characterized AP-1 DNA-binding activity in nuclear extracts prepared from v-fos- and c-fos-transformed rat fibroblast cell lines and v-jun-transformed chicken embryo fibroblasts under various growth conditions. During proliferation, the level of AP-1 DNA-binding activity does not differ among the v-fos, c-fos, or v-jun-transformed cells and their normal progenitors, despite constitutive overexpression of the corresponding oncoproteins. Therefore, although necessary, it is not likely that an increase in DNA binding is sufficient for fos or jun transformation. Normal rat and chicken fibroblasts demonstrate very low levels of AP-1 DNA-binding activity when quiescent, and upon serum stimulation a biphasic increase is observed. A similar cyclical pattern is seen in v-fos-transformed cells, but in v-jun-transformed cells AP-1 DNA-binding activity does not fluctuate in response to serum stimulation, which suggests that this level of control may be exerted through the Jun component of the AP-1 complex.
 ...
PMID:Transformation by the fos or jun oncogene does not increase AP-1 DNA-binding activity. 835 Apr 8

Commitment of HL-60 cells to macrophage or granulocytic differentiation was achieved by incubation with 4 beta-phorbol 12-myristate 13-acetate (PMA) for 30-60 min or with dimethyl sulphoxide (DMSO) for 24 h respectively. The commitment stage towards PMA-induced macrophage differentiation was associated with increases in jun B and c-fos mRNA levels, as well as with an increase in the binding activity of transcription factor AP-1. Nevertheless, gel retardation analysis indicated that the AP-1 activity detected in untreated cells was drastically reduced during the commitment stage of DMSO-induced HL-60 differentiation towards granulocytes. When HL-60 cells were treated with sodium butyrate, which induced monocytic differentiation, a remarkable increase in AP-1 binding activity was detected. Treatment of HL-60 cells with 1 alpha,25-dihydroxyvitamin D3, another monocytic differentiation agent, induced a weak, but appreciable, increase in AP-1 activity. Furthermore, addition of sodium butyrate or 1 alpha,25-dihydroxyvitamin D3 to HL-60 cells induced the expression of c-fos, c-jun, jun B and jun D proto-oncogenes. In contrast, when HL-60 cells were treated with retinoic acid, a granulocytic differentiation inducer, no enhanced AP-1 binding activity was observed, and only a weak increase in jun D mRNA level was detected. These data indicate that formation of AP-1 is not required for the induction of HL-60 differentiation towards granulocytes, whereas induction of monocytic differentiation is correlated with an increase in AP-1 activity. The differential expression of AP-1 activity may be critical in the differentiation of HL-60 cells towards monocytic or granulocytic lineages.
 ...
PMID:Differences in expression of transcription factor AP-1 in human promyelocytic HL-60 cells during differentiation towards macrophages versus granulocytes. 836 64

Terminal differentiation and cell proliferation are in many cases, as in muscle cells, mutually exclusive processes. While differentiating myoblasts are withdrawn from the cell cycle, myogenesis is inhibited by some mitogens and overexpression of some oncogenes, including proto-oncogene c-fos (which expresses a growth-associated protein constituting the regulatory factor AP-1 in conjunction with c-Jun). MyoD, a muscle-specific transcription factor of the basic helix-loop-helix family, acts at both levels because it triggers a muscle differentiation programme in non-muscle cells, and induces a complete block of cell proliferation. Antagonistic interaction between MyoD and c-Jun has been demonstrated. We here show that c-fos expression greatly decreases upon muscle cell differentiation, concomitant with MyoD-induced activity. We have identified a MyoD-binding site overlapping with the serum-responsive element in the c-fos promoter. We demonstrate that MyoD can act as a negative regulator for c-fos transcription by blocking serum responsiveness through this binding site. These data suggest that the MyoD negative effect on cell growth could be partly mediated by transcriptional inactivation of growth-responsive genes.
 ...
PMID:Repression of c-fos promoter by MyoD on muscle cell differentiation. 841 25

Previous studies have demonstrated that human HL-60 myeloid leukemia cells differentiate in response to phorbol esters. This event is associated with induction of the c-jun early response gene and appearance of a monocytic phenotype. The present studies have examined the effects of vincristine-selected, multidrug resistance on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced HL-60 cell differentiation. The results demonstrate that multidrug-resistant HL-60 cells, designated HL-60/vinc, fail to respond to TPA with an increase in c-jun transcripts or other phenotypic characteristics of monocytic differentiation. By contrast, treatment of HL-60/vinc cells with okadaic acid, an inhibitor of serine/threonine protein phosphatases, induces c-jun transcription, growth arrest, and expression of the c-fms gene. Studies were also performed with an HL-60/vinc revertant (HL-60/vinc/R) line that has regained partial sensitivity to vincristine. The finding that HL-60/vinc/R cells respond to TPA with induction of a monocytic phenotype, but not c-jun expression, suggests that c-jun induction is not obligatory for monocytic differentiation. Other studies further demonstrate that the jun-B and fra-1 genes are induced by TPA in both HL-60/vinc and HL-60/vinc/R cells, whereas c-fos expression is attenuated in the HL-60/vinc line. Since TPA activates protein kinase C (PKC), we examined translocation of PKC from the cytosol to the membrane fraction. Although HL-60 and HL-60/vinc/R cells demonstrated translocation of PKC activity, this subcellular redistribution was undetectable in HL-60/vinc cells. Activity of the mitogen-activated protein kinase family with associated phosphorylation of c-Jun Y-peptide was markedly diminished in TPA-treated HL-60/vinc cells, but not in response to okadaic acid. Taken together, these findings suggest that vincristine resistance confers insensitivity to TPA-induced differentiation and can include defects in PKC-mediated signaling events and induction of jun/fos early response gene expression.
 ...
PMID:Defective translocation of protein kinase C in multidrug-resistant HL-60 cells confers a reversible loss of phorbol ester-induced monocytic differentiation. 838 57

NF-kappa B and AP-1 represent distinct mammalian transcription factors that target unique DNA enhancer elements. The heterodimeric NF-kappa B complex is typically composed of two DNA binding subunits, NF-kappa B p50 and NF-kappa B p65, which share structural homology with the c-rel proto-oncogene product. Similarly, the AP-1 transcription factor complex is comprised of dimers of the c-fos and c-jun proto-oncogene products or of closely related proteins. We now demonstrate that the bZIP regions of c-Fos and c-Jun are capable of physically interacting with NF-kappa B p65 through the Rel homology domain. This complex of NF-kappa B p65 and Jun or Fos exhibits enhanced DNA binding and biological function via both the kappa B and AP-1 response elements including synergistic activation of the 5' long terminal repeat of the human immunodeficiency virus type 1. These findings support a combinatorial mechanism of gene regulation involving the unexpected cross-coupling of two different classes of transcription factors to form novel protein complexes exhibiting potentiated biological activity.
 ...
PMID:Cross-coupling of the NF-kappa B p65 and Fos/Jun transcription factors produces potentiated biological function. 840 56


<< Previous 1 2 3 4 5 6 7 8 9 10