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)

Naturally occurring (programmed) cell death in the developing brain has morphological characteristics of apoptosis and is associated with internucleosomal DNA fragmentation. Apoptosis also plays a role in cell death following hypoxia-ischaemia in the developing rat brain. Ionizing radiation-induced cell death in the brain of the young rat has morphological characteristics of apoptosis, is mediated by protein synthesis and is associated with internucleosomal DNA fragmentation. Methyl-azoxymethanol (MAM) acetate injection in the young rat produces apoptotic cell death in the external granule cell layer of the cerebellum. In addition, strong c-Jun immunore-activity is observed in apoptotic cells during normal development and following experimentally induced cell death. Moreover, c-Jun mRNA induction and de novo c-Jun protein synthesis, together with activation of c-Jun/AP-1, as revealed with gel mobility shift assay, occurs in irradiated animals. Western blotting of total brain homogenates shows a c-Jun-immunoreactive band at p39, which corresponds to the molecular weight of c-Jun, in control rats. However, a thick c-Jun-immunoreactive band at about p62, accompanied by a decrease of the p39 band, occurs in irradiated and MAM-treated rats. A thin band immediately above the thick p62 band, suggestive of c-Jun phosphorylation, is also observed in treated rats. Taken together, these observations indicate that c-Jun expression is associated with apoptotic cell death in the developing central nervous system.
Neuropathol Appl Neurobiol 1996 Dec
PMID:Cell death in the normal developing brain, and following ionizing radiation, methyl-azoxymethanol acetate, and hypoxia-ischaemia in the rat. 900 34

Since the PAD gene (also called promoter of Alzheimer's disease amyloid A4 precursor gene or amyloid beta-protein precursor promoter) has two AP-1 consensus sequences, and members of the Fos and Jun families are the major components of the transcription factor activator protein-1 (AP-1), we have investigated the localization of c-Fos and c-Jun immunoreactivity and its relationship to beta-amyloid deposition in the brains of patients with Alzheimer's disease and amyloid angiopathy. c-Jun, but not c-Fos, immunoreactivity is observed in the muscular layer of meningeal and cerebral blood vessels with amyloid angiopathy, and in the soma of glial cells and cellular processes of unknown origin surrounding beta-amyloid deposits in the brain. These results show that c-Jun may participate in the cascade of events leading to increased beta-APP (beta-amyloid precursor protein) production and beta-amyloid deposition in the brains of patients with Alzheimer's disease and amyloid angiopathy.
Neuropathol Appl Neurobiol 1996 Dec
PMID:Amyloid deposition is associated with c-Jun expression in Alzheimer's disease and amyloid angiopathy. 900 42

Studies were carried out to explore how extracellular matrix molecules, such as fibronectin (FN), promote capillary endothelial (CE) cell growth. When G0-synchronized cells were plated on FN-coated dishes, expression of the immediate-early mRNAs, c-fos, c-myc and c-jun, was rapidly induced, even in the absence of serum or soluble growth factors. Moreover, plating cells on different FN densities (5-200 micrograms/150 mm dish), resulted in a dose-dependent increase in the steady state levels of these mRNAs. Addition of FGF potentiated gene activation and was required for maximal DNA synthesis, however, the overall steady-state level of gene induction was dictated primarily by the density of immobilized FN. Expression of junB also was induced when suspended cells bound RGD-peptide coated microbeads that promote integrin clustering, but not when the suspended cells bound beads coated with other receptor ligands (e.g. acetylated low density protein) or when they were stimulated by soluble FN or FGF in the absence of substrate adhesion. c-Jun exhibited a similar requirement for gene induction except that it also was partially induced by binding to soluble FN alone. In contrast, c-fos expression was induced by all stimuli tested. Interestingly, inhibition of Na+/H+ exchange using hexamethylene-amiloride prevented most of the FN-induced increase in c-jun expression whereas it was relatively ineffective when cells were simultaneously stimulated by both FN and FGF. These data demonstrate that cell adhesion to extracellular matrix and associated integrin binding can directly activate signaling cascades in quiescent CE cells that lead to induction of immediate-early genes associated with the G0/G1 transition and thereby, stimulate these cells to reenter the growth cycle.
J Cell Sci 1996 Dec
PMID:Integrin-dependent induction of early growth response genes in capillary endothelial cells. 901 33

A high concentration (50 micrograms/ml) of gamma-linolenic acid (GLA) induced morphological lesions typical of apoptosis, as well as DNA fragmentation, in HeLa cells. A lower concentration of GLA (20 micrograms/ml), caused an increased proliferating cell nuclear antigen (PCNA) labelling, with 92.7% cells positive, compared to 27.7% at a concentration of 50 micrograms/ml GLA. In correlation with these results, the number of cells with degraded DNA below the G0/G1 peak increased significantly in the 50 micrograms/ml GLA-treated cells, but increased only slightly in cells exposed to the lower level of GLA. The high levels of PCNA induced by 20 micrograms/ml GLA, in both G1 and S phases, may indicate a state of DNA repair synthesis, whilst at the higher concentration of GLA, most of the cells became apoptotic. Since apoptosis is associated with the deregulation of c-Myc expression, and as the Raf-1-MAP kinase cascade activates the expression of c-Myc and c-Jun, we investigated the effects of 20 and 50 micrograms/ml GLA on the Raf-1, c-Myc and c-Jun levels, and on the activity of MAP kinase. The results showed that 50 micrograms/ml GLA lowered the activity of MAP kinase. As expected with the decreased MAP kinase activity in the cells exposed to the higher level GLA, the c-Jun levels were also lowered. The levels of c-Myc, however, were increased. It is therefore possible that the deregulated expression of c-Myc in the HeLa cells exposed to the high level of GLA (50 micrograms/ml) may contribute to the induction of apoptosis in HeLa cells.
Prostaglandins Leukot Essent Fatty Acids 1996 Dec
PMID:The induction of apoptosis in human cervical carcinoma (HeLa) cells by gamma-linolenic acid. 901 18

Pituitary adenylate-cyclase-activating polypeptide (PACAP) has been shown to possess mitogenic activity in various tumor cells. The present study was designed to investigate signal transduction mechanisms and expression of the proto-oncogenes c-fos and c-jun linked to the mitogenic effect of PACAP in the pancreatic carcinoma cell line AR4-2J. PACAP-(1-27)-peptide and PACAP-(1-38)-peptide, but not the structurally related vasoactive intestinal polypeptide (VIP), potently stimulated [3H]thymidine incorporation and cell number at doses of 0.1-10 nM. Both molecular forms of PACAP strongly increased formation of cAMP and inositol trisphosphate, elevated cytosolic Ca2+ levels and induced mitogen-activated protein (MAP) kinase activity. Quantitative reverse-transcription PCR revealed that PACAP-(1-27)-peptide and PACAP-(1-38)-peptide elevated c-fos mRNA levels 50-100-fold, whereas c-jun mRNA levels increased only moderately (2-3-fold). The effect of PACAP on c-fos and c-jun expression in AR4-2J cells was rapid (20 min), transient (1-2 h), dose-dependent IC50, 0.5 nM) and was abolished by the specific PACAP receptor antagonist PACAP-(6-38)-peptide or inhibitors of protein kinase C or tyrosine kinases. Compared with PACAP, epidermal growth factor and gastrin equipotently stimulated c-fos transcription whereas VIP, secretin, forskolin or phorbolester showed only marginal effects. Both PACAP (1-27)-peptide and PACAP-(1-38)-peptide strongly increased the DNA binding activity of the c-fos/ c-jun heterodimer transcription factor AP-1 at 10 nM and also stimulated AP-1 transcriptional activity up to 20-fold in AR4-2J cells. These findings indicate that the mitogenic effect of PACAP mediated via activation of the GTP-binding protein coupled PACAP/VIP-1 (PV1) receptor is linked to the MAP kinase cascade, increased expression of the proto-oncogenes c-fos and c-jun and activation of the heterodimeric transcription factor AP-1.
Eur J Biochem 1996 Dec 15
PMID:Pituitary adenylate-cyclase-activating polypeptide stimulates proto-oncogene expression and activates the AP-1 (c-Fos/c-Jun) transcription factor in AR4-2J pancreatic carcinoma cells. 902 70

We investigated the expression of inducible transcription factors (ITFs) and the fate of medial septal (MS) cholinergic neurons following fornix fimbria (FF) transection c-Jun, but not c-Fos or Krox 24 was induced in nerve growth factor receptor-immunoreactive (NGFr-ir), parvalbumin-negative MS neurons by 48 h and still highly expressed 2 months after transection. JunD was expressed only at 48 h after transection. Levels of choline acetyl transferase immunoreactivity (ChAT-ir) and NGFr-ir decreased substantially 7 and 14 days respectively following FF transection and remained depressed for up to 2 months. We also investigated other measures of nerve cell death and found that there was a time-dependent loss of cresyl violet staining, but no evidence of DNA fragmentation, acidophilia or clusterin expression in the MS region. There was however, good evidence of microglial activation and astrocyte hypertrophy in the MS. These results suggest that axotomized c-Jun-positive septohippocampal neurons lose their cholinergic phenotype but do not die for up to 2 months after FF transection. The function of c-Jun in axotomized MS neurons remains a mystery, but c-Jun expression alone is clearly not sufficient to elicit death of these neurons.
Brain Res Mol Brain Res 1996 Dec 31
PMID:Medial septal cholinergic neurons express c-Jun but do not undergo DNA fragmentation after fornix-fimbria transections. 903 13

Motor neuron diseases in humans, which include amyotrophic lateral sclerosis (ALS) and spinal muscular atrophies (SMAs), are characterized by motorneuron loss and chromatolysis in some or many remaining cells of the anterior horn of the spinal cord. Motorneurons are filled with phosphorylated neurofilaments, and ubiquitinated filamentous and granular inclusions which conform Lewy-like bodies in ALS patients. In addition, axonal balloonings filled with phosphorylated neurofilaments are usually observed in ALS patients with predominant signs of spinal motor neuron deficits and rapid clinical course. SMAs also occur in other species. Loss of motorneurons and chromatolytic cells filled with phosphorylated neurofilaments are the main pathologic findings in the ventral horn. In both humans and animals, loss of synaptic afferents is found in chromatolytic cells but not in normally-appearing motorneurons, thus suggesting that loss of synapses is a later event in motor neuron disease. These morphological features, together with the lack of c-Jun/AP-1 immunostaining and lack of staining with the method of in situ labelling of nuclear DNA fragmentation of dying cells, are different from those found during the process of naturally occurring (programmed) cell death in normal development. Although deletions in the SMN and NAIP genes located in 5q are found in patients with SMA, the cell death programme in SMA should not be considered as a mere persistence or reactivation of naturally occurring (programmed) cell death during normal development.
Neurologia 1996 Dec
PMID:[Motor neuron diseases: a type of programmed cell death?]. 904 76

At least three mitogen-activated protein kinase (MAPK) cascades were identified in mammals, each consisting of a well-defined three-kinase module composed of a MAPK, a MAPK kinase (MAPKK), and a MAPKK kinase (MAPKKK). These cascades play key roles in relaying various physiological, environmental, or pathological signals from the environment to the transcriptional machinery in the nucleus. One of these MAPKs, c-Jun N-terminal kinase (JNK), stimulates the transcriptional activity of c-Jun in response to growth factors, proinflammatory cytokines, and certain environmental stresses, such as short wavelength UV light or osmotic shock. The JNKs are directly activated by the MAPKK JNKK1/SEK1/MKK4. However, inactivation of the gene encoding this MAPKK by homologous recombination suggested the existence of at least one more JNK-activating kinase. Recently, the JNK cascade was found to be structurally and functionally conserved in Drosophila, where DJNK is activated by the MAPKK DJNKK (hep). By a database search, we identified an expressed sequence tag (EST) encoding a portion of human MAPKK that is highly related to DJNKK (hep). We used this EST to isolate a full-length cDNA clone encoding a human JNKK2. We show that JNKK2 is a highly specific JNK kinase. Unlike JNKK1, it does not activate the related MAPK, p38. Although the regulation of JNKK1 activities and that of JNKK2 activities could be very similar, the two kinases may play somewhat different regulatory roles in a cell-type-dependent manner.
Mol Cell Biol 1997 Dec
PMID:Molecular cloning and characterization of human JNKK2, a novel Jun NH2-terminal kinase-specific kinase. 937 71

We have investigated whether lithium has effects on transcription factor binding to consensus DNA sequences of AP-1 and cyclic AMP-responsive element (CRE) in cultured rat neurons and in vivo. Treatment of rat cerebellar granule cells (CGC) with lithium chloride induced a concentration-dependent increase in AP-1 and CRE binding activities with maximal effects at therapeutically relevant concentrations of 0.5 and 1.0 mM. Time-course studies show that lithium's effects on AP-1 and CRE binding were biphasic within the first 24 h of treatment in immature CGC in culture and persistent in mature CGC, lasting as long as 7 days. These actions were concurrent with an increase in the mRNA levels of c-fos and c-jun, as well as the protein levels of c-Fos, c-Jun, and phosphorylated CRE binding protein (p-CREB). Gel supershift assays using transcription factor-specific antibodies revealed that p-CREB, Jun D, and a Fos family protein(s) are components of the AP-1 binding complex in untreated and lithium-treated CGC. Chronic dietary treatment of rats with lithium carbonate for 4 weeks also significantly increased AP-1 and CRE binding activity in the frontal cortex, hippocampus, amygdala, and cerebellum. Similar to the results obtained in CGC, p-CREB, Jun D, and Fos family proteins are present in the AP-1 binding sites in the frontal cortex and hippocampus of untreated and lithium-treated rats. Lithium-induced activation of transcription factor binding to AP-1 and CRE sites in vivo and in vitro provides a new avenue to study the mechanisms of action of lithium in the treatment of manic depressive illness.
J Neurochem 1997 Dec
PMID:Lithium increases transcription factor binding to AP-1 and cyclic AMP-responsive element in cultured neurons and rat brain. 937 64

The ras proto-oncogene is frequently mutated in human tumors and functions to chronically stimulate signal transduction cascades resulting in the synthesis or activation of specific transcription factors, including Ets, c-Myc, c-Jun, and nuclear factor kappa B (NF-kappaB). These Ras-responsive transcription factors are required for transformation, but the mechanisms by which these proteins facilitate oncogenesis have not been fully established. Oncogenic Ras was shown to initiate a p53-independent apoptotic response that was suppressed through the activation of NF-kappaB. These results provide an explanation for the requirement of NF-kappaB for Ras-mediated oncogenesis and provide evidence that Ras-transformed cells are susceptible to apoptosis even if they do not express the p53 tumor-suppressor gene product.
Science 1997 Dec 05
PMID:Requirement of NF-kappaB activation to suppress p53-independent apoptosis induced by oncogenic Ras. 938 87


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