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)

We investigated the effect of hypoglycemic treatment on the activation of the AP-1 transcription factors and the regulation of basic fibroblast growth factor (bFGF) gene expression in multidrug resistant human breast carcinoma MCF-7/ADR cells. Northern blot and gel mobility shift assays showed that hypoglycemic treatment induced c-jun and c-fos gene expression, AP-1 binding activity, as well as bFGF gene expression. Moreover, transfected cells expressing high levels of abnormal c-Jun protein exhibited a reduction in the bFGF protein levels compared to parental cells. A potent protein kinase C (PKC) inhibitor, H-7 (60 micrograms/ml) suppressed the stress-induced bFGF gene expression. Our study also demonstrated that H-7 did not facilitate the decay of bFGF mRNA. Thus, the suppression of bFGF gene expression by treatment with H-7 was due to the effect of the drug on the synthesis of bFGF mRNA rather than the stability of bFGF mRNA. Our data suggest that hypoglycemia-induced bFGF gene expression is mediated through the activation of PKC and the AP-1 transcription factors.
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PMID:Hypoglycemia-induced AP-1 transcription factor and basic fibroblast growth factor gene expression in multidrug resistant human breast carcinoma MCF-7/ADR cells. 870 Jan 61

Relatively little is known about molecular genetic events that participate in the genesis and progression of hemangiopericytoma. In this study, we describe two cases of hemangiopericytoma accompanied by severe hypoglycemia. Tumor cells from patient 1 exhibited insulin-growth factor I (IGF I) and insulin-like growth factor I receptor (IGF IR) mRNA transcripts. Tumor cells from patient 2 exhibited IGF II, IGF IR and IGF binding proteins 1-3 mRNA. Serum from patient 2 contained IGF II, mostly in a large molecular form ("big" IGF II); the IGF II level did not change after the tumor removal. The presence of IGF IR in tumor cells was confirmed by immunoprecipitation with antibodies that recognize human IGF IR subunit (visualized as a 460-kDa band). The hemangiopericytoma cells derived from patient 1 expressed 210000 IGF I receptors/cell. Specific binding of IGF I to the tumor cell membrane fraction was higher in tissue from patient 1, while the tissue of patient 2 showed relatively low IGF I binding. In contrast, IGF II binding was much higher in tissue from patient 2. Both tumor tissues showed positive immunostaining for c-Jun; one tumor showed strong immunostaining for c-Myc, H-Ras and p53, while the other exhibited strong reaction with H-Ras antibodies only. No loss of the heterozygosity at the genes APC, NFI and nm23-H1 loci in tumor tissue obtained from patient 1 was found. In effect, our results suggest multiple molecular genetic changes in hemangiopericytoma -- activation of some oncogenes and the IGF growth factor family. IGF ligands together with IGF IR could be responsible for hypoglycemia and perhaps the transformed phenotype.
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PMID:Molecular pathology of hemangiopericytomas accompanied by severe hypoglycemia: oncogenes, tumor-suppressor genes and the insulin-like growth factor family. 969 37

Physiological conditions like hypoxia or hypoglycemia trigger expression of VEGF, a key regulator of angiogenesis. To elucidate the molecular mechanism underlying the VEGF regulation of hypoglycemia, we investigated the role of AP-1 transcription factor subunits c-Jun and JunB. Using c-jun(-/-) and junB(-/-) mouse embryonic fibroblasts, we demonstrate that both c-Jun and JunB are required for the hypoglycemia-mediated induction of VEGF expression. This process is independent of the master regulator of hypoxic stress HIF-1, as HIF expression and stabilization are not affected by the loss of AP-1 subunits. Analysis of signaling cascades regulating c-Jun and/or JunB activity and/or transcription upon hypoglycemia by application of specific inhibitors of protein kinase C (PKC) or extracellular signal-regulated kinase (ERK) signaling revealed that hypoglycemia-mediated induction of c-Jun is regulated via a PKCalpha-dependent signaling pathway. In contrast, JunB is activated by the MAP kinase ERK for the AP-1 subunits c-Jun and JunB to mediate VEGF regulaltion of hypoglycemia.
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PMID:c-Jun and JunB are essential for hypoglycemia-mediated VEGF induction. 1734 24

This review tries to survey the expression patterns of inducible transcription factors (ITFs) of the Jun (c-Jun, JunB, JunD) and Fos (c-Fos, FosB, Fra) families as well as of zinc finger proteins (Krox-20 and Krox-24) and their mRNAs following ischemia, epileptic seizures, hypoglycemia, axotomy and(programmed) neuronal death in the mammalian brain. Jun and Fos proteins or Jun/Fos-containing transcription complexes are also termed as AP-I proteins or AP-1 complexes. So far, however, the genes encoding for Jun, Fos and Krox proteins have been included into the rather heterogeneous pool of immediate-early genes (IEGs). Therefore, we suggest the term 'inducible transcription factors' (ITF) with regard to their main functional features: (rapid) inducibility and control of transcription. In the first part of the review, we summarize the current knowledge on the organization and control of the jun, fos and krox promoters as well as about the molecular down-stream effects of their proteins. In the sections on general and focal ischemia, epileptic seizures and hypoglycemia. the review is focused on the formation of specific expression patterns that is the individual temporo-spatial expression of different ITFs following the same pathophysiological stimulus. Particular emphasis is put on the correlation of ITF expression with vulnerability and resistance of specific neuronal subpopulations. Furthermore, we have also reviewed the DNA-binding activity of AP-1 proteins in the adult rat brain and the pool of putative effector proteins following the above-mentioned stimulation paradigms. Subsequently, the less defined role of ITFs in the process of (programmed) neuronal death is discussed. The last section surveys the prolonged and selective expression of c-Jun in axotomized neurons and its relation to the expression of nitric oxide synthase.
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PMID:Neuronal expression of AP-1 proteins in excitotoxic-neurodegenerative disorders and following nerve fiber lesions. 2644 38