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

The response of the kidney to ischemic injury includes increased DNA synthesis, which is preceded by rapid and brief expression of the c-fos proto-oncogene. While the timing of these two events would suggest that c-Fos participates in an immediate-early gene program leading to proliferation, no direct test of this hypothesis exists. The purpose of these studies was (1) to determine whether c-fos is expressed as part of a typical immediate-early (IE) gene response, which would require co-expression of c-jun and sensitivity to cycloheximide, and (2) to determine whether the cells expressing c-Fos are the same as those undergoing DNA synthesis. Northern analysis was performed on renal mRNA at different times following release of a 50 minute period of renal hilar clamping. c-jun and c-fos mRNA were rapidly and briefly expressed following renal ischemia and their expression was superinduced by cycloheximide in a manner typical of an immediate-early gene response. 3H-thymidine autoradiography performed on semi-thin sections from intravascularly perfusion fixed kidneys 24 hours following induction of ischemia showed labeled nuclei in cells lining the damaged proximal tubules of the outer stripe of the outer medulla, as well as proximal tubules in the cortex and interstitial cells throughout the kidney. However, immunohistochemical localization of c-Fos and c-Jun protein occurred predominantly in nuclei of the thick ascending limb, distal tubule and collecting duct cells. The studies demonstrate that c-fos and c-jun are expressed following renal ischemia as a typical immediate-early gene response, but they are expressed in cells that do not enter the cell cycle. The failure of the cells to enter the cell cycle may depend on the co-expression of jun-B and jun-D, which suppress the mitogenic activity of c-Jun in other cells. The data suggest that the IE response following renal ischemia is part of the stress response, which is antiproliferative rather than proliferative. The role of the stress response during renal ischemia and the fate of the cells undergoing it are unknown.
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PMID:DNA synthesis is dissociated from the immediate-early gene response in the post-ischemic kidney. 854 1

The transcription factor AP-1, made up of dimers of Fos and Jun proto-oncogene products, is involved in distinct cellular processes, including cell proliferation, differentiation and apoptosis. In this study, we have used mice in which both copies of the c-fos gene were disrupted by targeted mutagenesis in order to analyze how the apoptotic response was affected in these mice. We prepared primary cultures from the lymphoid organs, spleen and thymus, obtained from both wild-type and c-fos -/- mice and analyzed the induction of apoptosis in these cultures in the absence and presence of etoposide, an inducer of apoptosis in distinct cell types. Primary cultures from both organs, spleen and thymus, isolated from wild-type mice underwent apoptosis after 3 and 6 h of culture, respectively. Addition of etoposide enhanced the apoptotic response and c-fos mRNA levels in both spleen and thymic cells. Nevertheless, we found that induction of apoptosis in primary cultures of cells obtained from spleen and thymus of c-Fos-deficient mice was practically identical to that observed in wild-type mice. These results demonstrate that c-Fos is not essential for apoptosis and that cells lacking c-Fos may undergo normal apoptosis.
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PMID:C-Fos is not essential for apoptosis. 857 44

AP-1 is an ubiquitous transcription factor which is composed of the Jun and Fos proto-oncogene proteins and is thought to play a role in both cell proliferation and differentiation. We have used an immortal, bipotential oligodendrocyte-type-2 astrocyte progenitor cell line (O-2A/c-myc) which can differentiate into oligodendrocytes or type-2 astrocytes in vitro, to investigate whether AP-1 DNA-binding activity fluctuates during glial cell differentiation. Unexpectedly, DNA-mobility shift assays using a TRE-containing oligonucleotide derived from the promoter of the glial-specific gene, glial fibrillary acidic protein (GFAP/AP-1), revealed that O-2A/c-myc progenitor cells were devoid of conventional AP-1 DNA-binding complexes. O-2A/c-myc cells did however contain several novel GFAP/AP-1-specific DNA-binding complexes, which we have termed APprog. APprog complexes recognise the TRE consensus motif present in the GFAP/AP-1 oligonucleotide together with adjacent 3' sequences but do not contain c-Jun or any other known Jun-related proteins. When O-2A/c-myc cells underwent terminal differentiation APprog complexes were lost and conventional AP-1 DNA-binding activity became evident, particularly in astrocytes. These changes appear to be closely linked to the differentiation process since they did not occur in a derivative of the O-2A/c-myc cell line that contains an activated v-ras oncogene and which fails to differentiate under appropriate culture conditions. The inverse regulation of conventional AP-1 and APprog complexes within the O-2A lineage suggests that these factors may play a role in the regulation of glial cell differentiation or glial cell-specific gene expression.
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PMID:Differential regulation of AP-1 and novel TRE-specific DNA-binding complexes during differentiation of oligodendrocyte-type-2-astrocyte (O-2A) progenitor cells. 857 97

The proto-oncogene product c-Fos, a component of the transcription factor AP-1, plays a critical role in the expression of genes required for cellular proliferation and differentiation. The c-Fos is induced in early B lineage cells developed in the interleukin-7-dependent bone marrow (BM) cell culture from normal mice. In order to investigate a role of the c-Fos in early B cell development, we have used BM cells from two different transgenic mice carrying the exogenous c-fos gene controlled by the promoter of the H-2Kb gene (H2-c-fos) or the interferon alpha/beta (IFN)-inducible Mx gene (Mx-c-fosD). Development of B lineage cells was retarded in the BM cell culture from H2-c-fos mice. Although B lineage cells normally developed in the BM cell culture from Mx-c-fosD mice without IFN stimulation, the development was completely blocked in the Mx-c-fosD culture when transgenic c-fos was induced in BM cells by IFN stimulation. Furthermore, the IL-7-dependent proliferation of B lineage cells in Mx-c-fosD BM cells was also suppressed by the induction of c-Fos. These results suggest that the c-Fos plays a role as a negative regulator in the early B cell development.
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PMID:A regulatory role of c-Fos in the development of precursor B lymphocytes mediated by interleukin-7. 861 96

v-erbA is the oncogenic form of the c-erbA proto-oncogene, which encodes the receptor for thyroid hormones. The expression of the v-erbA oncogene in thyroid differentiated cells, PC Cl 3, inhibits iodide uptake and thyrotropin-dependent growth, whereas it has no effect on the expression of the other thyroid specific markers, i.e. thyroglobulin, thyroperoxidase and thyrotropin receptor. The activity of transcription factor AP-1, evaluated by a specific DNA binding assay and by transcription of AP-induced promoter (TRE) is enhanced in PC v-erbA cells. v-erbA mutants in the DNA binding domain do not affect the iodide uptake of thyroid cells nor AP-1 activity. We suggest that this transcriptional activation mediates the selective effects of v-erbA on the expression of thyroid specific markers.
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PMID:The v-erbA oncogene selectively inhibits iodide uptake in rat thyroid cells. 864 48

Specific binding of nuclear proteins to the region of transcriptional attenuation has been shown to modulate the expression of c-myb, a nuclear proto-oncogene preferentially expressed in lympho-hematopoietic cells. Here, it plays an important role in processes of differentiation and proliferation. The mechanism that regulates c-myb expression is not yet fully understood. The block of transcriptional elongation which has been mapped to a 1 kb region within murine intron 1 may represent one regulatory pathway. The DNA sequences containing the transcriptional pause site are well conserved between murine and human species, thus Implying similar transcription-control strategies. We compared the binding potential of nuclear extracts (from human fibroblasts and MOLT4 as well as murine NIH3T3- and 70Z/3B- cell lines) to oligonucleotide sequences previously shown to be target binding sites in the murine system. One complex containing a 70 D protein was found to be associated specifically with transcriptionally active leukemia cells. We performed transient expression studies with a CAT reporter construct containing this putative enhancer sequence and yielded significant CAT activity. We identified further a putative 20 kD repressor protein in transcriptionally silent cells and demonstrated that c-Jun is part of an ubiquitously present complex. Our results confirm the participation of intron 1 in transcriptional regulation of the c-myb gene (in mouse and human) and implicate multiple and complex regulatory mechanisms of activation during myelomonocytic differentiation and leukemic cell growth control.
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PMID:c-myb intron I protein binding and association with transcriptional activity in leukemic cells. 868 83

Apigenin, a low-toxic and non-mutagenic plant flavonoid, suppresses 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-mediated tumour promotion of mouse skin. TPA has the ability to activate protein kinase C (PKC) and induce proto-oncogene expression. Our study shows that apigenin inhibits PKC by competing with ATP, and exhibits an IC50 value of 10 +/- 0.5 microM. Apigenin also reduces the level of TPA-stimulated phosphorylation of cellular proteins. Of the protein tyrosine kinases tested, the fibroblast growth factor (FGF) receptor was most strongly affected by apigenin (IC50 20 microM), and pp60v-src most weakly affected (IC50 > 200 microM). Treatment of NIH 3T3 cells with 100 ng/ml TPA and 10, 50 and 100 microM apigenin resulted in 50, 80 and 100% suppression of TPA-induced C-JUN expression, respectively. Treatment of TPA with 10 microM apigenin inhibited TPA-induced C-FOS expression. TPA-stimulated cell growth was suppressed by 25 microM apigenin. Our results provide some evidence for understanding apigenin's inhibitory effects of TPA-mediated tumour promotion.
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PMID:Inhibitions of protein kinase C and proto-oncogene expressions in NIH 3T3 cells by apigenin. 869 23

The proto-oncogene c-jun encodes a component of the AP-1 transcription-activating complex and has been implicated in the regulation of diverse cellular processes, including cell proliferation, differentiation, transformation, and most recently, apoptosis. We have used a U937 monocytic leukemia cell line stably expressing a c-jun dominant-negative, transactivation-domain deletion mutant (TAM67) to assess the role of c-jun in apoptotic events induced by exposure to the antimetabolite 1-beta-D-arabinofuranosylcytosine (ara-C). Mutant cells produce a truncated M(r) 29,000 protein that interferes with the function of normal c-Jun (and c-Fos) proteins through a quenching mechanism. Parental U937, cells expressing TAM67, and cells carrying only the empty vector (pMM) were exposed to ara-C for 6 h, and apoptosis was monitored by cell morphology as well as qualitative and quantitative assays of DNA damage. No differences in apoptosis could be detected between the three cell lines at any of the ara-C concentrations evaluated. In addition, ara-C concentrations > or = 1.0 x 10(-6) M were equally inhibitory to the clonogenic growth of U937 and TAM67-expressing cells. In contrast, lower concentrations of ara-C (i.e., < 5.0 x 10(-7) M) were significantly less inhibitory to mutant U937 cell colony formation than to their parental counterparts. The reduced sensitivity of TAM67-expressing cells to low concentrations of ara-C could not be attributed to biochemical or cytokinetic factors, since the two cell lines were indistinguishable with respect to 1-beta-D-arabinofuranosylcytosine 5'-triphosphate (ara-CTP) formation, ara-CTP:dCTP ratios, and S-phase fraction. However, a significantly lower percentage of TAM67-expressing cells exposed to submicromolar concentrations of ara-C exhibited features associated with a differentiated monocytoid phenotype (i.e., increased plastic adherence and CD11b expression) compared to their parental counterparts. Lower concentrations of ara-C were also significantly less effective in decreasing the percentage of S-phase cells and in down-regulating c-myc mRNA levels in the mutant line, events associated with induction of leukemic cell differentiation. Finally, ara-C-induced up-regulation of c-jun message and protein was markedly attenuated in TAM67-expressing cells, findings consistent with a c-jun dominant-negative model. Collectively, these findings suggest that dysregulation of c-jun in U937 cells antagonizes low-dose ara-C-mediated cellular maturation but does not prevent higher concentration of this agent from triggering apoptosis. They also raise the possibility that separate aspects of the antiproliferative actions of ara-C may be differentially regulated by c-jun.
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PMID:Effect of 1-beta-D-arabinofuranosylcytosine on apoptosis and differentiation in human monocytic leukemia cells (U937) expressing a c-Jun dominant-negative mutant protein (TAM67). 873 70

The proto-oncogene product c-Fos, a component of the transcription factor AP-1, is induced in early B lineage cells. In order to investigate a role of the c-Fos in early B cell development, fetal liver (FL) cells from transgenic mice carrying an IFN-inducible c-fos gene (Mx-c-fos) were cultured on a stromal cell layer with IL-7. The development was perturbed by the addition of IFN at the beginning of culture. When IFN was added in the FL culture after B lineage cells developed, pro-B (B220+, CD43+) cells were selectively dying by apoptosis within 48 h after IFN stimulation. These results suggest that c-Fos plays a causal role in deletion of pro-B cells.
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PMID:[Overexpression of c-Fos induces apoptosis of CD43+ pro-B cells]. 874 81

The proto-oncogene product c-Fos, a component of the transcription factor AP-1, is induced in early B lineage cells. To investigate a role of c-Fos in early B cell development, fetal liver (FL) cells from transgenic mice carrying an IFN-alphabeta (IFN)-inducible c-fos gene (Mx-c-fosD) were cultured on a stromal cell layer with IL-7. Although B lineage cells normally developed in the Mx-c-fosD FL cell culture, the development was perturbed by the addition of IFN at the beginning of culture. When IFN was added in the FL culture after B lineage cells developed, pro-B (B220+,CD43+) cells were selectively dying by apoptosis within 48 h after IFN stimulation. This apoptosis was intrinsically induced in the pro-B cells that overexpressed c-fos when the Mx-c-fosD FL (H-2Kb) cells were cocultured with the normal C3H FL (H-2Kk) cells. The molecular basis of the apoptosis was investigated by examining expression of the genes that regulate apoptosis. The IFN stimulation did not modulate expression of Bcl-2 and Fas in early B lineage cells from the Mx-c-fosD FL culture. However, Rag-2 was down-regulated in these cells within 12 h after IFN stimulation. These results suggest that the c-Fos plays a causal role in deletion of pro-B cells with nonfunctional Ag receptor.
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PMID:Overexpression of c-Fos induces apoptosis of CD43+ pro-B cells. 889 9


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