• Journal of Life Science
• /
• v.27 no.8
• /
• pp.857-863
• /
• 2017

The FBJ murine osteosarcoma viral oncogene homolog B (FosB) gene is located at chromosome 19, and encodes 43 Kda protein. Functionally, the FosB gene is important for differentiation, development, and pathogenesis. Furthermore, the FosB gene is suggested as possible biomarker for tracing disease prognosis. In this study, we constructed plasmid containing a FosB promoter region and evaluate its promoter activity. We analyzed the putative promoter region in FosB genomic DNA using bioinformatics program, and we found important regulatory elements in 1 Kb upstream from transcription start site (TSS). Therefore, we performed polymerase chain reaction (PCR) amplification on region from-1,555 upstream to +73 of the FosB genomic DNA, and PCR product was inserted into TA vector to create the $TA-1^{st}FosBp$ plasmid. We then prepared the primer sets, which contain a restriction enzyme site for Kpn1 and Nhe1, in order to reinsert into the TA vector to prepare $TA-2^{nd}FosBp$ plasmid. It was finally subcloned into pGL3-luc vector after enzyme cutting. To evaluate whether the cloned plasmid is useful in cell based experiment, we performed luciferase assay with pGL3-FosBp-luctransfection. FosB promoter activity was increased compared to empty vector, and this activity was significantly increased by treatment of doxorubicin and taxol. We obtained consistent data on regulation of FosB gene expression after anticancer drug treatment using Western blot analysis. The results suggest that promoter cloning of the human FosB gene is very useful for studying gene expression and analyzing biomarkers.

• Journal of Life Science
• /
• v.30 no.12
• /
• pp.1070-1077
• /
• 2020

Treatment with anticancer drugs changes the expression of multiple genes related to cell proliferation, migration, and drug resistance. These changes in gene expression may be connected to regulatory networks for each other. This study showed that doxorubicin treatment induces the expression of oncogenic FosB and decreases the expression of oncogenic SETDB1 in A549 and H1299 human lung cancer cells, which are different in tumor suppressor p53 status. However, a small difference was detected in the quantitative expression of those proteins in the two kinds of cells. To examine the potential regulation of SETDB1 and FosB by p53, we predicted putative p53 binding sites on the genomic DNA of SETDB1 and FosB using a TF motif binding search program. These putative p53 binding sites were identified as 18 sites in the promoter regions of SETDB1 and 21 sites in the genomic DNA of FosB. A luciferase assay confirmed that p53 negatively regulated the promoter activities of SETDB1 and FosB. Furthermore, the results of RT-PCR, western blot, qPCR, and immunostaining experiments indicated that the transfection of exogenous p53 decreases the expression of SETDB1 and FosB in H1299 cells. This indicates that p53 negatively regulates the expression of SETDB1 and FosB at the transcriptional level. Collectively, the downregulation of SETDB1 and FosB by p53 may provide functional networks for apoptosis and for the survival of cancer cells during anticancer drug treatment.

• BMB Reports
• /
• v.49 no.4
• /
• pp.238-243
• /
• 2016

The efficacy of anticancer drugs depends on a variety of signaling pathways, which can be positively or negatively regulated. In this study, we show that SETDB1 HMTase is down-regulated at the transcriptional level by several anticancer drugs, due to its inherent instability. Using RNA sequence analysis, we identified FosB as being regulated by SETDB1 during anticancer drug therapy. FosB expression was increased by treatment with doxorubicin, taxol and siSETDB1. Moreover, FosB was associated with an increased rate of proliferation. Combinatory transfection of siFosB and siSETDB1 was slightly increased compared to transfection of siFosB. Furthermore, FosB was regulated by multiple kinase pathways. ChIP analysis showed that SETDB1 and H3K9me3 interact with a specific region of the FosB promoter. These results suggest that SETDB1-mediated FosB expression is a common molecular phenomenon, and might be a novel pathway responsible for the increase in cell proliferation that frequently occurs during anticancer drug therapy.

• Journal of Acupuncture Research
• /
• v.20 no.3
• /
• pp.131-140
• /
• 2003

Objective : The purpose of this study is to investigate the effect of Panax ginseng Radix herb-acupuncture on c-fos expression in each area of the hippocampus of acutely ethanol-intoxicated rats. Methods : Twenty-four male Sprague-Dawley tats were divided into untreated(normal), ethanol-treated(control), Panax ginseng Radix-treated(sample A), ethanol-and Panax gingseng Radix-treated(sample B) groups. Each group was evaluated by the changes of c-fos-positive neurons in each area of the hippocampus by using and image analyzer and microscope. Results : 1. In the CA1 area, the number of c-fos-positive neurons in the control group was diminished compared with the normal group. The number of c-fos-positive neurons in the sample B group had no marked difference from the control group. 2. In the CA2-3 area, the number of c-fos-positive neurons in the control group was diminished compared with the normal group, The number of c-fos-positive neurons in the sample B group was increased compared with the control group. 3. In the Dentate gyrus area, the number of c-fos-positive neurons in the control group was diminished compared with the normal group. The number of c-fos-positive neurons in the sample B group was increased compared with the control group. Conclusions : These results indicate that, c-fos expression in each area of the hippocampus was reduced in ethanol-intoxicated group. Treatment of Panax ginseng Radix herb-acupuncture increased this diminution. Panax ginseng Radix could be able to effect on the prevention of the amnesia and learning disability in alcoholism.

• The Korean Journal of Physiology and Pharmacology
• /
• v.5 no.4
• /
• pp.299-305
• /
• 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.

• Molecules and Cells
• /
• v.42 no.12
• /
• pp.884-892
• /
• 2019

Piperlongumine (PL), a natural alkaloid compound isolated from long pepper (Piper longum), can selectively kill cancer cells, but not normal cells, by accumulation of reactive oxygen species (ROS). The objective of this study was to investigate functional roles of expression of SETDB1 and FosB during PL treatment in MCF7 breast cancer cells. PL downregulates SETDB1 expression, and decreased SETDB1 expression enhanced caspase 9 dependent-PARP cleavage during PL-induced cell death. PL treatment generated ROS. ROS inhibitor NAC (N-acetyl cysteine) recovered SETDB1 expression decreased by PL. Decreased SETDB1 expression induced transcriptional activity of FosB during PL treatment. PARP cleavage and positive annexin V level were increased during PL treatment with FosB overexpression whereas PARP cleavage and positive annexin V level were decreased during PL treatment with siFosB transfection, implying that FosB might be a pro-apoptotic protein for induction of cell death in PL-treated MCF7 breast cancer cells. PL induced cell death in A549 lung cancer cells, but molecular changes involved in the induction of these cell deaths might be different. These results suggest that SETDB1 mediated FosB expression may induce cell death in PL-treated MCF7 breast cancer cells.

• Journal of Acupuncture Research
• /
• v.23 no.3
• /
• pp.37-45
• /
• 2006

Objectives : The study was conducted to investigate the effect of Deakumeumja herb-acupuncture on c-Fos expression in each area of the hippocampus of Alcohol intoxicated rats. Methods : Experimental groups were divided into five groups ; normal group, the alcohol-treated (control) group, the alcohol- 1 mg/kg Daekumeumja treated (sample A) group, the alcohol- 5 mg/kg Daekumeumja treated (sample B) group, the alcohol- 10 mg/kg Daekumeumja treated (sample C) group (n = 6 for each group). Rats of normal group were injected intraperitoneally with saline once a day for 5 consecutive days, while animals of the alcohol-treated (control) group were injected once a day with 2 g/kg of alcohol for the same duration of time. Animals of the alcohol and Daekumeumja-treated (sample A, B, C) groups were acupunctured at Chung-wan$(CV_{12})$ with 2 g/kg of alcohol and the appropriate amount of Daekumeumja extract once a day for 5 days. Each groups was evaluated by the changes of c-fos-positive neurons in each area of the hippocampus by using an image analyzer and microscope. Results: 1. In the CAI region of the hippocampus, the number of Fos-positive cells in the sample B, C groups were significantly increased compared with the control group. 2. In the CA2-3 regions of the hippocampus, the number of Fos-positive cells of the sample B, C groups were significantly increased compared with the control group. 3. In the Dentate gyrus region of the hippocampus, the number of Fos-positive cells of the sample C group was significantly increased compared with the control group. Conclusion : c-fos expression in each area of the hippocampus was reduced in alcohol-intoxicated groups. Treatment of Daekumeumja increased this reduction. In conclusion, it can be suggested that Daedumeumja possesses protective effects of the amnesia and learning disability in alcoholism.

• ETRI Journal
• /
• v.29 no.3
• /
• pp.259-269
• /
• 2007

The ubiquitous flexible operating system (UbiFOS) is a real-time operating system designed for cost-conscious, low-power, small to medium-sized embedded systems such as cellular phones, MP3 players, and wearable computers. It offers efficient real-time operating system services like multi-task scheduling, memory management, inter-task communication and synchronization, and timers while keeping the kernel size to just a few to tens of kilobytes. For flexibility, UbiFOS uses various task scheduling policies such as cyclic time-slice (round-robin), priority-based preemption with round-robin, priority-based preemptive, and bitmap. When there are less than 64 tasks, bitmap scheduling is the best policy. The scheduling overhead is under 9 ${\mu}s$ on the ARM926EJ processor. UbiFOS also provides the flexibility for user to select from several inter-task communication techniques according to their applications. We ported UbiFOS on the ARM9-based DVD player (20 kB), the Calm16-based MP3 player (under 7 kB), and the ATmega128-based ubiquitous sensor node (under 6 kB). Also, we adopted the dynamic power management (DPM) scheme. Comparative experimental results show that UbiFOS could save energy up to 30% using DPM.

• BMB Reports
• /
• v.32 no.6
• /
• pp.594-598
• /
• 1999

The Jun and Fos families of eukaryotic transcription factors form heterodimers capable of binding to their cognate DNA enhancer elements. We are interested in searching for inhibitors or antagonists of the binding of the Jun-Fos heterodimer to the activator protein-1 (AP-1) site. The basic-region leucine zipper (bZIP) domain of c-Fos was expressed as a fusion protein with glutathione S-transferase, and allowed to form a heterodimer with the bZIP domain of c-Jun. The heterodimer was bound to glutathione-agarose, to which were added radiolabeled AP-1 nucleotides. After thorough washing, the gel-bound radioactivity was counted. The assay is faster than the coventional electrophoretic mobility shift assay because the gel electrophoresis step and the autoradiography step are eliminated. Moreover, the assay is very sensitive, allowing the detection of picomolar quantities of nucleotides, and is not affected by up to 50% dimethylsulfoxide, a solvent for hydrophobic inhibitors. Curcumin and dihydroguaiaretic acid, recently known inhibitors of Jun-Fos-DNA complex formation, were applied to this Jun-GST-fused Fos system and revealed to decrease the dimer-DNA binding.

• BMB Reports
• /
• v.47 no.8
• /
• pp.451-456
• /
• 2014

Parthenolide, a natural product derived from Feverfew, prevents septic shock and inflammation. We aimed to identify the effects of parthenolide on the RANKL (receptor activator of $NF-{\kappa}B$ ligand)-induced differentiation and bone resorbing activity of osteoclasts. In this study, parthenolide dose-dependently inhibited RANKL-mediated osteoclast differentiation in BMMs, without any evidence of cytotoxicity and the phosphorylation of p38, ERK, and $I{\kappa}B$, as well as $I{\kappa}B$ degradation by RANKL treatment. Parthenolide suppressed the expression of NFATc1, OSCAR, TRAP, DC-STAMP, and cathepsin K in RANKL-treated BMMs. Furthermore, parthenolide down-regulated the stability of c-Fos protein, but could not suppress the expression of c-Fos. Overexpression of NFATc1 and c-Fos in BMMs reversed the inhibitory effect of parthenolide on RANKL-mediated osteoclast differentiation. Parthenolide also inhibited the bone resorbing activity of mature osteoclasts. Parthenolide inhibits the differentiation and bone-resolving activity of osteoclast by RANKL, suggesting its potential therapeutic value for bone destructive disorders associated with osteoclast-mediated bone resorption.