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Query: UNIPROT:P06889 (Mol)
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Exposure of rodents to light at daily times at which it can phase-shift circadian rhythms (subjective night) induces an increase in immunoreactivity for the immediate-early gene product Fos in cells of the circadian pacemaker, the suprachiasmatic nuclei (SCN). Light exposure at other phases (subjective day) does not increase Fos immunoreactivity in SCN cells, but it is not known whether this failure reflects the inability of light to induce transcription of appropriate mRNAs, or a post-transcriptional block. We used in situ hybridization studies to examine levels of mRNA in the SCN of rats exposed to light during the subjective day and subjective night. We studied levels of mRNAs for several immediate-early genes: c-fos, NGFI-A, NGFI-B, c-jun, junB and junD, before and after light exposure at these phases. Levels of mRNAs for all of the genes tested were unaffected by light exposure during the subjective day, and all were increased in response to light during the subjective night. With the exception of a weak constitutive label for junD, none of the genes were expressed in the SCN in darkness at either phase. Light-induced increases in the levels of several mRNAs in the SCN occur only during the subjective night; the mechanisms which prevent such responses during the subjective day remain unknown.
Brain Res Mol Brain Res 1992 Jun
PMID:Circadian variation in photic regulation of immediate-early gene mRNAs in rat suprachiasmatic nucleus cells. 132 9

Regulation of corticotropin-releasing hormone (CRH) gene expression in vivo was assessed via in situ hybridization histochemistry, using probes directed against an intronic sequence of the CRH gene. Initial characterization of the CRH intron (CRHin) probe revealed specific localization of signal to the nuclear compartment of neurons in the medial parvocellular paraventricular hypothalamus, which are known to produce CRH peptide and mRNA. Abundance of CRHin signal was low, commensurate with a low resting pool of CRH heteronuclear RNA (hnRNA), representing CRH primary transcript. Regulation of CRH hnRNA levels was assessed after acute glucocorticoid synthesis blockade by injection of metyrapone. Metyrapone inhibits the conversion of 11-deoxycorticosterone to corticosterone, thereby rapidly depleting glucocorticoids and serving as a discrete stimulus for hypothalamo-pituitary-adreno-cortical activation. Plasma hormone measurements verified the efficacy of treatment, as metyrapone-treated rats showed extremely low basal corticosterone levels at all postinjection time points, while exhibiting progressive increases in plasma ACTH release over the 60-min postinjection period. CRH hnRNA levels were markedly increased 15-30 min after metyrapone injection, consistent with a rapid induction of CRH gene transcription in response to the stimulatory event. CRH mRNA, on the other hand, did not exceed control levels until 60 min post metyrapone, illustrative of a temporal lag between transcriptional changes and detectable changes in mRNA pools. Additional sections from metyrapone-and vehicle-treated rats were hybridized with probes complementary to mRNA encoding the immediate-early gene c-fos. c-fos was not present under unstimulated conditions yet was rapidly induced upon metyrapone treatment or vehicle injection (15 min).(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1992 Jul
PMID:Rapid regulation of corticotropin-releasing hormone gene transcription in vivo. 132 19

Human cytomegalovirus (HCMV) is an important pathogen of the lung. We determined whether the HCMV immediate early genes (IE1 and IE2) can alter the regulation of the cellular immediate early genes (c-fos and c-myc). Plasmid constructs containing the promoter-regulatory regions c-myc or c-fos upstream of the reporter gene, chloramphemicol acetyl transferase, were co-transfected into T cells (Jurkat cells), monocytes/macrophages (THP-1 cells), or human fibroblast cells with plasmid constructs containing the promoter-regulatory region of the HCMV IE genes upstream of the bona fide IE1, IE2 or IE+2 genes; a plasmid that contained no IE coding region was used as a control. These studies show that both products of the HCMV IE genes markedly upregulated expression of the cellular c-fos and c-myc genes. The viral effects of individual proteins (IE1 or IE2) were dependent both on the promoter-regulatory region of the cellular gene and the cell type. In all cells, the combination of IE1 and IE2 further upregulated both cellular genes, suggesting a synergistic effect of IE1 with IE2. Both of the c-myc promoters (P1 and P2) were up-regulated by the HCMV IE gene products. IE1 and IE2 also upregulated the cells' endogenous c-myc and c-fos genes, as determined by amounts of the respective mRNAs. These studies show that HCMV can markedly alter cellular IE gene expression and that the effects of HCMV IE1 and IE2 proteins are dependent both on the promoter-regulatory region of the cellular gene and the type of cell in which the interaction occurs.
Am J Respir Cell Mol Biol 1992 Sep
PMID:The immediate early genes of human cytomegalovirus upregulate expression of the cellular genes myc and fos. 132 8

An elevated expression of c-fos protooncogene, encoding transcription factor Fos, is known to serve as a useful marker of neuronal activation. In the studies reported in this communication we have used Northern and dot blot techniques to analyze c-fos mRNA levels in male rat brain during the learning of the copulatory behavior. The animals were trained (single ejaculation in a training/testing session) for up to 7 sessions. C-fos mRNA levels have been found to increase in the sensory cortex area following the third and fifth session but not after the first and the last one.
Brain Res Mol Brain Res 1992 Aug
PMID:Delayed c-fos expression in sensory cortex following sexual learning in male rats. 132 98

Activation of either muscarinic cholinergic or thrombin receptors increases phosphoinositide turnover, Ca2+ mobilization, and redistribution of protein kinase C and induces rapid transient increases in c-fos mRNA and c-jun mRNA in 1321N1 cells. To determine whether the increases in c-fos and c-jun mRNA induced by carbachol and thrombin are sufficient to stimulate AP-1-mediated transactivation, 1321N1 cells were transfected with a reporter carrying two copies of the tetradecanoyl phorbol acetate response element and the firefly luciferase gene. Thrombin was significantly more effective than carbachol at stimulating AP-1-mediated transactivation. To identify the factors underlying the difference in AP-1 activity induced by carbachol and thrombin, members of the fos and jun families which encode components of AP-1 were examined. Carbachol and thrombin have similar effects on expression of c-fos, fosB, fra-2, junB, and junD, both acutely and over a 24-h time course. However, whereas carbachol leads only to transient induction of c-jun (maximal at 0.5 h), thrombin induces a biphasic increase in c-jun mRNA--an initial peak at 0.5 h and a second, more-prolonged increase at 12 h. Thrombin but not carbachol also induces a late increase in fra-1 mRNA, which peaks at 12 h. The secondary increase in c-jun mRNA is associated with marked increases in c-Jun protein levels and AP-1 DNA-binding activity. The late induction of c-jun and fra-1 mRNA can be prevented by adding the antagonist hirudin 30 min after thrombin, which results in loss of thrombin-stimulated increases in c-Jun protein, AP-1 DNA-binding activity, and AP-1-mediated transactivation. These findings suggest that rapid and transient conduction of c-fos and c-jun mRNA is insufficient to induce prominent changes in gene transcription, while the sustained increase in c-jun mRNA and perhaps the late induction of fra-1 mRNA are required for generation of AP-1 DNA-binding activity and transactivation through AP-1.
Mol Cell Biol 1992 Oct
PMID:Biphasic increase in c-jun mRNA is required for induction of AP-1-mediated gene transcription: differential effects of muscarinic and thrombin receptor activation. 132 61

We have previously reported on the presence of a CArG motif at -100 in the Rous sarcoma virus long terminal repeat which binds an avian nuclear protein termed enhancer factor III (EFIII) (A. Boulden and L. Sealy, Virology 174:204-216, 1990). By all analyses, EFIII protein appears to be the avian homolog of the serum response factor (SRF). In this study, we identify a second CArG motif (EFIIIB) in the Rous sarcoma virus long terminal repeat enhancer at -162 and show only slightly lower binding affinity of the EFIII/SRF protein for this element in comparison with c-fos serum response element (SRE) and EFIII DNAs. Although all three elements bind the SRF with similar affinities, serum induction mediated by the c-fos SRE greatly exceeds that effected by the EFIII or EFIIIB sequence. We postulated that this difference in serum inducibility might result from binding of factors other than the SRF which occurs on the c-fos SRE but not on EFIII and EFIIIB sequences. Upon closer inspection of nuclear proteins which bind the c-fos SRE in chicken embryo fibroblast and NIH 3T3 nuclear extracts, we discovered another binding factor, SRE-binding protein (SRE BP), which fails to recognize EFIII DNA with high affinity. Competition analyses, methylation interference, and site-directed mutagenesis have determined that the SRE BP binding element overlaps and lies immediately 3' to the CArG box of the c-fos SRE. Mutation of the c-fos SRE so that it no longer binds SRE BP reduces serum inducibility to 33% of the wild-type level. Conversely, mutation of the EFIII sequence so that it binds SRE BP with high affinity results in a 400% increase in serum induction, with maximal stimulation equaling that of the c-fos SRE. We conclude that binding of both SRE BP and SRF is required for maximal serum induction. The SRE BP binding site coincides with the recently reported binding site for rNF-IL6 on the c-fos SRE. Nonetheless, we show that SRE BP is distinct from rNF-IL6, and identification of this novel factor is being pursued.
Mol Cell Biol 1992 Oct
PMID:Maximal serum stimulation of the c-fos serum response element requires both the serum response factor and a novel binding factor, SRE-binding protein. 132 62

The linkage between the transmembrane signal transduction system utilized by endothelin and alterations in gene expression has been investigated in C6 glioma cells. Treatment of C6 cells with endothelin-1 caused a rapid and transient 5-fold increase in c-fos and c-jun mRNA levels, followed by a decrease at 4 h. Dose-response studies indicated that 1 nM endothelin-1 caused half-maximal induction of c-fos mRNA 0.5 h after treatment and that maximal induction was elicited with a concentration of 10 nM. Actinomycin D totally abolished the rapid increase in c-fos mRNA caused by endothelin, indicating that the effect is at the transcriptional level. Endothelin-1 caused a decrease in proenkephalin mRNA to 50% of control levels at 4 h after treatment and had no effect on histone H4 mRNA over a 24 h period that was examined. These data indicate that receptor binding of endothelin-1 leads to rapid changes in the expression of immediate-early response genes which may cause more prolonged changes in the expression of AP-1 and/or CREB target genes in the nervous system.
Brain Res Mol Brain Res 1992 Jul
PMID:Stimulation of c-fos and c-jun gene expression and down-regulation of proenkephalin gene expression in C6 glioma cells by endothelin-1. 133 50

Intraocular injection of kainate into the rabbit eye causes both a translocation and transport of the bipolar cell's alpha PKC 6 h later. Although this effect is similar to what occurs for the phorbol ester, phorbol 12,13-dibutyrate (PDbut), it shows specificity in that N-methyl-D-aspartate (NMDA), 5,7-dihydroxytryptamine and 2-amino-4-phosphonobutyrate (APB) are ineffective. However, preliminary experiments suggest that, when injected into the eye, quisqualate also influences the alpha PKC of the bipolar cells. Injection of kainate into the rabbit eye shows that c-fos-like protein is expressed in certain amacrine and ganglion but not in bipolar cells 6 h later. This expression of c-fos immunoreactivity is transient because 15 h after the injection of kainate no positive staining was seen. It was not possible to analyse the kainate-induced c-fos expression for periods of less than 6 h because the anaesthetic used, Hypnorm, induced c-fos-like protein expression which lasted for 2-4 h.
Brain Res Mol Brain Res 1992 Sep
PMID:An intraocular injection of kainate induces expression of c-fos-like protein and activation of protein kinase C (alpha) in specific rabbit retinal neurones. 133 56

The products of the cellular immediate-early genes (IEGs) are thought to act as messengers in the coupling of trans-synaptic stimuli with altered neuronal gene expression. However, the manner in which neurotransmission specifies particular responses through the IEGs is undefined. In this report, mRNA and transcription analysis of a precisely-timed, physiological IEG response illustrates how an IEG signal may be organized through differential neurotransmitter receptor activation. The nocturnal pattern of IEG expression in the rat pineal gland has been shown to be differentially regulated through post-synaptic adrenergic receptors. Induction of the c-fos gene is primarily mediated through alpha 1-receptors, whereas the coordinately regulated jun-B gene exhibits dual regulation through alpha 1- and beta-receptors. A simultaneous repression of c-jun expression is partly mediated through a beta-receptor mechanism. In vitro analysis of IEGs in cultured pineal glands has confirmed the receptor-specific link between adrenergic neurotransmission and IEG induction. The pineal is a unique neuroendocrine model in which the characteristics and function of the IEG third messenger system may be defined.
Brain Res Mol Brain Res 1992 Nov
PMID:Neurotransmitter-stimulated immediate-early gene responses are organized through differential post-synaptic receptor mechanisms. 133 88

A Fos-lacZ transgenic mouse has been described that accurately recapitulates both constitutive and inducible patterns of c-fos expression in adult mice. Here we describe the developmental expression of the transgene in the brain during the early postnatal period. On the day of birth, expression of the transgene is observed in several discrete regions of the CNS; including the olfactory bulb, hippocampus, retrosplenial cortex, parafascicular nucleus of the thalamus, and several cranial nerve nuclei. In these regions, expression declines to adult levels by three weeks. In other regions of the CNS, expression appeared transiently after P0.
Brain Res Mol Brain Res 1992 Nov
PMID:Temporal and spatial expression of a fos-lacZ transgene in the developing nervous system. 133 94


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