• Title/Summary/Keyword: c-fos gene

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Role of Calcium Influx in mediating the TRH-induced c-fos Gene Expression (갑상선자극 분비 호르몬에 의해 유도되는 c-fos 유전자 발현에서 Ca2+의 역할에 관한 연구)

  • Seung Kirl Ahn;Don
    • The Korean Journal of Zoology
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    • v.36 no.4
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    • pp.487-495
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    • 1993
  • TRH (Thvrotropin-Releasing Hormone) known to regulate the transcription of the TSH (Thyroid-Stimulating Hormones gene in pituitary cells, but little is understood about the mechanism(sl involved. re present study was attempted to elucidate the role of Ca2+ movement through the voltage-gated channels in the regulation of TSH gene transcription. The c-fos is one of immediate early genes and used as model system for the investigation of signaling pathwavs involved in various stimuli. The changes of c-fos mRNA levels were determined after treatment of various agents using Northern and slot hybridization analysis. The c-fos mRNA was rapidly and transiently induced by TRH (about 3-fold) in GH3 cells and this induction was repressed by calcium chelating agent (EGTA), calcium channel blocker (verapamil) anti protein kinase C inhibitor (aminoacridine). The abilities of forskolin (adenvlate cvclase activators, PMA (protein kinase C activator), and A23187 (calcium ionophore) to affect c-ios gene transcription, either alone or in combination with TRH were tested in the same cells. All of them significantly increased the level of c-fos mRUA. However, no additive relationship was observed in all combined treatments except forskolin. These results suggest that TRH action on the c-fos gene activation is mediated by calcium influx as well as through protein kinase C.

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Expression of Multidrug Resistance-associated Protein (MRP), c-myc and c-fos in L1210 Cells (L1210 암세포에서 Multidrug Resistance-associated Protein (MRP), c-myc 및 c-fos 유전자의 발현양상)

  • Kim, Seong-Yong
    • Journal of Yeungnam Medical Science
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    • v.14 no.1
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    • pp.67-76
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    • 1997
  • The occurrence of multidrug resistance (MDR) is one of the main obstacles in the successful chemotherapeutic treatment of cancer. In this study The gene expressions of multidrug resistance-associated protein (MRP), c-myc and c-fos were investigated in L1210 cells. Adriamycin- or vincristine-resistant L1210 cells, L1210AdR or L1210VcR, respectively, has been identified to overexpression of mdr1 gene. The expression leve of MRP gene in L1210AdR and L1210Cis was more decreased than that in L1210 cells. The c-myc and c-fos genes were expressed both in L1210 and resistant sublines. In L1210AdR, the expressions level of c-myc and c-fos genes were decreased than in L1210. However, in L1210VcR and L1210Cis, c-myc and c-fosgene expressionwere rather increased than L1210. These results suggested that MRP does not contribute in resistance of drug-resistant L1210 cells and there is no relations between MRP and mdr1 gene expression. The expression of c-myc and c-fos gene may be changed during transformation of L1210 to drug-resistant sublines.

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Effect of Protein Kinase C Inhibitor (PKCI) on Radiation Sensitivity and c-fos Transcription Activity (Protein Kinase C Inhibitor (PKCI)에 의한 방사선 민감도 변화와 c-fos Proto-oncogene의 전사 조절)

  • Choi Eun Kyung;Chang Hyesook;Rhee Yun-Hee;Park Kun-Koo
    • Radiation Oncology Journal
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    • v.17 no.4
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    • pp.299-306
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    • 1999
  • Purpose : The human genetic disorder ataxia-telangiectasia (AT) is a multisystem disease characterized by extreme radiosensitivity. The recent identification of the gene mutated in AT, ATM, and the demonstration that it encodes a homologous domain of phosphatidylinositol 3-kinase (PI3-K), the catalytic subunit of an enzyme involved in transmitting signals from the cell surface to the nucleus, provide support for a role of this gene in signal transduction. Although ionizing radiation was known to induce c-fos transcription, nothing is known about how ATM or PKCI mediated signal transduction pathway modulates the c-fos gene transcription and gene expression. Here we have studied the effect of PKCI on radiation sensitivity and c-fos transcription in normal and AT cells. Materials and Methods: Normal (LM217) and AT (AT5BIVA) cells were transfected with PKCI expression plasmid and the overexpression and integration of PKCI was evaluated by northern blotting and polymerase chain reaction, respectively. 5 Gy of radiation was exposed to LM and AT cells transfected with PKCI expression plasmid and cells were harvested 48 hours after radiation and investigated apoptosis with TUNEL method. The c-fos transcription activity was studied by performing CAT assay of reporter gene after transfection of c-fos CAT plasmid into AT and LM cells. Results: Our results demonstrate for the first time a role of PKCI on the radiation sensitivity and c-fos expression in LM and AT cells. PKCI increased radiation induced apoptosis in LM cells but reduced apoptosis in AT cells. The basal c-fos transcription activity is 70 times lower in AT cells than that in LM cells. The c-fos transcription activity was repressed by overexpression of PKCI in LM cells but not in AT cells. After induction of c-fos by Ras protein, overexpression of PKCI repressed c-fos transcription in LM cells but not in AT cells Conclusion: Overexpression of PKCI increased radiation sensitivity and repressed c-fos transcription in LM cells but not in AT cells. The results may be a. reason of increased radiation sensitivity of AT cells. PKCI may be involved in an ionizing radiation induced signal transduction pathway responsible for radiation sensitivity and c-fos transcription. The data also provided evidence for novel transcriptional difference between LM and AT cells.

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Parallel Regulation of Prolactin and c-fos Gene Expression by 17$\beta$-estradiol and Stress in the Mouse Pituitary

  • Kim, Ji-Eune;Ko, Ji-Yun;Kim, Young-il;Yoon, Yong-Dal;Cho, Byung-Nam
    • Animal cells and systems
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    • v.4 no.1
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    • pp.71-76
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    • 2000
  • The aim of this study was to investigate expression patterns of the prolactin (PRL) and c-fos genes by 17$\beta$-estradiol (17$\beta$-E) and stress in the mouse pituitary. In the pituitary, the levels of PRL mRNA were found high with some fluctuation at 30, 50, and 90 min whereas the levels of PRL mRNA were low at 120 min when ovariectomized female mice were injected with 17$\beta$-E or vehicle. PRL mRNA levels began to increase again at 4 h and remained high up to 24 h only in the 17$\beta$-E- treated mice. The overall changes in c-fos mRNA by 17$\beta$-E were very similar to those in PRL mRNA in the pituitary. Subsequent study revealed that these high initial levels of PRL and c-fos mRNAs were caused by stress during Injection, not by 17$\beta$-E, since vehicle injection alone into the ovariectomized mice could increase the levels of PRL and c-fos mRNAs. The stress-induced elevations of PRL and c-fos mRNAs were inhibited by bromocriptin, a dopamine agonist, suggesting that the dopaminergic system is involved in the action route of injection stress. In addition, the induced levels of c-fos mRNA by 17$\beta$-E and stress in the pituitary were very low compared with those in the uterus. The time course changes in c-fos mRNA level were different between the pituitary and uterus. Taken together, these data indicate that PRL and c-tos gene expression in the pituitary are regulated by 17$\beta$-E and stress in a parallel manner, supporting the notion that c-Fos plays a role in regulation of PRL gene expression.

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Identification of GATA2 and AP-1 Activator Elements within the Enhancer VNTR Occurring in Intron 5 of the Human SIRT3 Gene

  • Bellizzi, Dina;Covello, Giuseppina;Di Cianni, Fausta;Tong, Qiang;De Benedictis, Giovanna
    • Molecules and Cells
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    • v.28 no.2
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    • pp.87-92
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    • 2009
  • Human SIRT3 gene contains an intronic VNTR enhancer. A T > C transition occurring in the second repeat of each VNTR allele implies the presence/absence of a putative GATA binding motif. A partially overlapping AP-1 site, not affected by the transition, was also identified. Aims of the present study were: 1) to verify if GATA and AP-1 sites could bind GATA2 and c-Jun/c-Fos factors, respectively; 2) to investigate whether such sites modulate the enhancer activity of the SIRT3-VNTR alleles. DAPA assay proved that GATA2 and c-Jun/c-Fos factors are able to bind the corresponding sites. Moreover, co-transfection experiments showed that the over-expression of GATA2 and c-Jun/c-Fos factors boosts the VNTR enhancer activity in an allelic-specific way. Furthermore, we established that GATA2 and c-Jun/c-Fos act additively in modulating the SIRT3-VNTR enhancer function. Therefore, GATA2 and AP-1 are functional sites and the T > C transition of the second VNTR repeat affects their activity.

No Role of Protected Region B of Human Cytochrome P4501A2 Gene (CYP1A2) As an AP-1 Response Element

  • Chung, In-Jae;Jung, Ki-Hwa
    • Archives of Pharmacal Research
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    • v.25 no.3
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    • pp.375-380
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    • 2002
  • Cytochrome P4501A2 (CYP1A2) is a member of the cytochrome P450 family of isozymes involved in the phase I drug metabolism of vertebrates. CYP1A2 is responsible for the activation of a number of aromatic amines to mutagenic and carcinogenic forms. Thus, the level of CYP1A2, which varies among different populations, may determine an individual's susceptibility to these chemicals. We have previously reported on the importance of a cis element named PRB (protected region B) in the regulation of human Cytochrome P4501A2 (CYP1A2) gene, which appeared to act as a positive regulatory element. Closer examination of the PRB sequence (-2218 to -2187 bp) revealed a putative AP-1 binding site, TGACTAA, at -2212 bp (Chung and Bresnick, 1997). To elucidate the role of AP-1 in CYP1A2 regulation, we transiently overexpressed c-Jun and c-Fos transcription factors in human hepatoma HepG2 cells, and examined their influence on the CYP1A2 promoter activity by reporter gene assays. Cotransfection of the c-Jun and the c-Fos expression vectors increased the induced transactivation by five to six fold from the CYP1A2 promoter constructs. However, deletion of the PRB element did not affect the degree of activation by the c-Jun and the c-Fos. Therefore, it is unlikely that the c-Jun and the c-Fos activate the CYP1A2 promoter through this AP-1 consensus-like sequence in the PRB region.

A Brief Introduction to the Transduction of Neural Activity into Fos Signal

  • Chung, Leeyup
    • Development and Reproduction
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    • v.19 no.2
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    • pp.61-67
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    • 2015
  • The immediate early gene c-fos has long been known as a molecular marker of neural activity. The neuron's activity is transformed into intracellular calcium influx through NMDA receptors and L-type voltage sensitive calcium channels. For the transcription of c-fos, neural activity should be strong enough to activate mitogen-activated protein kinase (MAPK) signaling pathway which shows low calcium sensitivity. Upon translation, the auto-inhibition by Fos protein regulates basal Fos expression. The pattern of external stimuli and the valence of the stimulus to the animal change Fos signal, thus the signal reflects learning and memory aspects. Understanding the features of multiple components regulating Fos signaling is necessary for the optimal generation and interpretation of Fos signal.

Sequence and Expression Analysis of c-fos Proto-oncogene in Korean Cattle (HANWOO) (한우 c-fos 유전자의 염기서열 및 발현분석)

  • Yu, S.L.;Chung, H.J.;Jung, K.C.;Lee, J.H.;Cho, K.W.;Choi, J.G.;Na, K.J.;Sang, B.C.
    • Journal of Animal Science and Technology
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    • v.45 no.6
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    • pp.891-900
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    • 2003
  • Cellular FOS(c-fos) protein is a transcription factor that forms heterodimers mostly with c-jun family and stimulates the transcription of genes containing AP-1 regulatory elements. This c-fos expression can control growth and differentiation of various precursor cells including myoblasts. The controls by c-fos gene have been identified for affecting skeletal muscle fiber traits which are the key determinants of meat quality in pigs. As a first step for identifying the relationship between c-fos gene and meat quality traits in cattle, we fully sequenced 1,443 bp of Hanwoo c-fos mRNA and analyzed expression patterns from various organs and muscle tissues. The sequence identities of Hanwoo c-fos with that of human, pig and mouse showed 89.8%, 93.3% and 87%, respectively. Analyses of the northern blot showed high c-fos expressions were obtained in spleen and rib muscle from 7 organs and 9 different parts of muscles investigated. These results presented here can be used as a valuable marker for meat quality related traits in cattle with further verification.

Regulation of Phosphorylated cAMP Response Element-Binding Protein, Fos-Related Antigen and FosB Expression by Dopamine Agonists in Rat Striatum

  • Choe, Eun-Sang;Kim, Jong-Yeon
    • The Korean Journal of Physiology and Pharmacology
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    • v.5 no.4
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    • pp.299-305
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    • 2001
  • Activation of D1-like dopamine receptors by psychostimulants, such as amphetamine, upregulates the expression of immediate early gene and opioid peptide gene in the striatum. The genomic changes are regulated by phosphorylated transcription factors via complicated intracellular events. To evaluate temporal expression of the transcription factors by dopaminergic stimulation, the D1-like dopamine agonist, amphetamine or SKF82958, was systematically delivered. As intracellular markers in response to the agonist, phosphorylated cAMP response element-binding protein (pCREB), Fos-related antigens (FRA) and FosB immunoreactivity (IR) was compared at 20 and 120 min time points in the selected areas of the striatum. Semi-quantitative immunocytochemistry showed that amphetamine (5 mg/kg, i.p.) significantly increased pCREB-IR at 20 min, sustained up to 60 min and decreased at 120 min after the infusion. Like amphetamine, the full D1 agonist, SKF82958 (0.5 mg/kg, s.c.), also increased pCREB-IR at 20 min, but not at 120 min after the infusion in the dorsal striatum (caudoputaman, CPu) and shell of ventral striatum (nucleus accumbens, NAc). In contrast, FRA- and FosB-IR induced by SKF82958 was significantly increased at 120 min, but not at 20 min after the administration. These data indicate that SKF82958 mimics induction of CREB phosphorylation by amphetamine and differentially regulates temporal induction of pCREB, and FRA and FosB expression in the striatum.

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Effect of Swimming Exercise of c-fos, c-jun Expression in Rat Hippocampus (흰쥐 해마에서 수영운동이 c-fos, c-jun 발현에 미치는 영향)

  • Lee, Sung-Ho
    • The Journal of the Korea Contents Association
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    • v.11 no.1
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    • pp.245-253
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    • 2011
  • This study is to examine the effect of swimming exercise on the expression of c-fos, c-jun protein in rat hippocampus. 4-weeks aged rats and 16-weeks aged rats were used in experimental materials. All of two groups were classified into control and swimming exercise group. Swimming exercise was practiced for an hour a day. The results were got as follows after practical application in 1 day, 3days, 7 days. The expression of c-fos, c-jun protein was increased in all of the two experimental groups significantly in 1 day, 3days, 7 days. It was increased gradually in order of after 1 day, 3days, 7 days. There seems to be the effect of swimming exercise increasing the expression of c-fos, c-jun protein in hippocampus. Therefore swimming exercise can improve cognitive function such as learning and memory and prevent through activating immediate - early gene by swimming exercise. And it seems to have the positive effect on growth and recovery of nerve.