• 미생물학회지
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• 제46권4호
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• pp.401-404
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• 2010

출아효모 Saccharomyces cerevisiae에서 RNA-binding 단백질인 Tho1은 mRNA가 전사되는 동안 초기 mRNA에 결합하여 mRNP 생성과 성숙한 mRNA의 핵에서 세포질로의 방출에 관여하는 것으로 여겨진다. 분열효모 Schizosaccharomyces pombe에서도 Tho1과 유사한 단백질을 암호화하는 유전자(spTho1로 명명)를 찾아 그 특성을 조사하였다. 이배체 S.pombe 균주에 하나의 spTho1 유전자만을 결실시킨 후 4분체분석을 수행한 결과, 이 유전자는 생장에 반드시 필요하지 않았다. 또한 spTho1 결실 돌연변이는 mRNA의 핵에서 세포질로의 방출도 정상적으로 보였다. 그러나 티아민에 의해 발현이 조절되는 강력한 프로모터를 이용하여 spTho1를 과발현시키면, 세포의 생장이 억제되었으며 $poly(A)^+$ RNA가 핵 안에 축적되었다. 이와 같은 결과들은 spTho1 유전자가 필수적이지는 않지만 mRNA의 핵에서 세포질로의 방출에 관여하고 있음을 시사한다.

• Molecules and Cells
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• 제28권1호
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• pp.67-71
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• 2009

Estrogen receptor ${\alpha}$ ($ER{\alpha}$) mediates the mitogenic effects of estrogen. $ER{\alpha}$ signaling regulates the normal growth and differentiation of mammary tissue, but uncontrolled $ER{\alpha}$ activation increases the risk to breast cancer. Estrogen binding induces ligand-dependent $ER{\alpha}$ activation, thereby facilitating $ER{\alpha}$ dimerization, promoter binding and coactivator recruitment. $ER{\alpha}$ can also be activated in a ligand-independent manner by many signaling pathways, including protein kinase A (PKA) signaling. However, in several $ER{\alpha}$-positive breast cancer cells, PKA inhibits estrogen-dependent cell growth. FoxH1 represses the transcriptional activities of estrogen receptors and androgen receptors (AR). Interestingly, FoxH1 has been found to inhibit the PKA-induced and ligand-induced activation of AR. In the present study, we examined the effects of PKA activation on the ability of FoxH1 to represses $ER{\alpha}$ transcriptional activity. We found that PKA increases the protein stability of FoxH1, and that FoxH1 inhibits PKA-induced and estradiol-induced activation of an estrogen response element (ERE). Furthermore, in MCF7 cells, FoxH1 knockdown increased the PKA-induced and estradiol-induced activation of the ERE. These results suggest that PKA can negatively regulate $ER{\alpha}$, at least in part, through FoxH1.

• 생명과학회지
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• 제16권6호
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• pp.1066-1070
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• 2006

Smooth muscle cell (SMC)의 증식은 혈관성장에 의한 질환의 발병기전의 중요한 요소이다. 혈관 손상 후 SMC의 성장조절에 대한 분자적 기작에 대한 연구는 치료제 개발에 있어 중요한 의미를 지닌다. 이에, 본 연구에서는 TNF family인 RANKL가 SMC의 증식을 촉진함을 입증하였다. RANKL는 p21의 발현을 감소시키고 p21의 promoter활성을 저해함으로써 SMC의 성장을 증가시켰다. 또한 ERK와 p38 MAPK의 활성이 RANKL에 의해 증가하였으며, ERK/p38의 저해제는 RANKL에 의해 유도되는 SMC의 성장을 완전히 억제하였다. 이러한 결과는 ERK와 p38 MAPK가 RANKL에 의해 유도되는 SMC의 증식에 중요한 역할을 함을 보여주는 것이다. 즉, RANK-RANKL-ERK/p38이 SMC의 증식을 매개하는 중요 분자이며, 이들 분자는 혈관 질환을 막는 새로운 치료제 개발의 표적분자가 될 수 있음이 입증되었다.

• The Korean Journal of Physiology and Pharmacology
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• 제7권5호
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• pp.261-266
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• 2003

Type 1 diabetes is an organ-specific autoimmune disease caused by the cytotoxic T cells-mediated destruction of the insulin-producing beta cells in the Langerhans pancreatic islets. Hepatocyte growth factor (HGF) is a potent mitogen and a promoter of proliferation of insulin producing beta cells of pancreatic islets. To study the role of HGF via viral vector in the development of streptozotocin (STZ)-induced diabetes in mice, we have developed an adenoviral vector genetically engineered to carry the gene for human HGF (hHGF) and evaluate the change of blood glucose, insulin level, and insulin-secreting beta cells of pancreatic islets. We demonstrate that the treatment with hHGF gene prevented the development of STZ-induced diabetes and increased serum insulin level to above normal range. Furthermore, it preserved pancreatic beta cells from destruction. These in vivo results may support previous findings that HGF is insulinotropic agent for beta cells and HGF treatment renders the cells to be resistant to the development of diabetes from STZ administration. We suggest that an adenoviral mediated hHGF gene therapy is a good candidate for the prevention and treatment of type 1 diabetes.

• BMB Reports
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• 제41권11호
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• pp.784-789
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• 2008

Mac-2BP is a ligand of the galectin family that has been suggested to affect tumor proliferation and metastasis formation. We assessed Mac-2BP expression at the transcriptional and translational levels to evaluate nerve growth factor (NGF)-induced Mac-2BP expression. A time kinetic analysis using reverse transcription-polymerase chain reaction showed that NGF-induced Mac-2BP transcript levels were 4-5 times higher than in controls. Mac-2BP enzyme-linked immunosorbent assay and immuno-fluorescence staining showed a 2-3-fold increase in intracellular and secreted Mac-2BP as a result of NGF stimulation. This increase was regulated by Akt activation and NF-${\kappa}B$ binding. p65 and p50-NF-${\kappa}B$ are major transcriptional factors in the Mac-2BP promoter region, and were shown to be regulated in accordance with the Akt activation states. Collectively, these results suggest that NGF induces Mac-2BP expression via the PI3K/Akt/NF-${\kappa}B$ pathway.

• 한국토양비료학회지
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• 제49권3호
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• pp.242-250
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• 2016

Veterinary antibiotics (VAs) has been used to treat animal disease and to increase animal weight as growth promoter. However, abused usage of VAs can cause production of antibiotic resistance genes (ARGs) in the environment and additionally, residual of VAs in soil can be transferred into crops. Therefore, main objective of this research was to examine bioaccumulation of VAs in sprouts (red cabbage, Brassica Olearacea L. var. Capitata f. rubra and red radish, Raphanus sativus) with hydroponic method. Total of 7 VAs in 2 different classes of VAs (tetracyclcines: tetracycline, oxytetracycline, chlortetracycline, sulfonamides: sulfamethoxazole, sulfamethazine, sulfamethiazole, macrolides: tylosin) were evaluated and experiment was conducted with solid phase extraction (SPE)/high performance liquid chromatography tandem mass spectrometry (HPLC/MS/MS). Initial spiked concentration of 7 VAs was $5mg\;L^{-1}$ and cultivation period was 8 days. Result showed that growth of sprouts was inhibited about 23-27% when VAs was introduced. Amount of bioaccumulated VAs was also differed depending on class of VAs. The highest amount of bioaccmulated VAs was tetracycline and sulfamethoxazole in each class with a concentration of 4.05, $7.73mg\;kg^{-1}$ respectively. Calculated transfer ratio of VAs into crops was also ranged 0.38-54.27%. Overall, bioaccumulation of VAs in crops can be varied depending on crop species and class of VAs. However, further research should be conducted to verify bioaccumulation of VAs in crops in the soil environment.

• Molecules and Cells
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• 제40권3호
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• pp.211-221
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• 2017

Transforming growth factor ${\beta}1$ $(TGF{\beta}1)/Smad4$ signaling plays a pivotal role in maintenance of the dynamic balance between bone formation and resorption. The microRNA miR-155 has been reported to exert a significant role in the differentiation of macrophage and dendritic cells. The goal of this study was to determine whether miR-155 regulates osteoclast differentiation through $TGF{\beta}1/Smad4$ signaling. Here, we present that $TGF{\beta}1$ elevated miR-155 levels during osteoclast differentiation through the stimulation of M-CSF and RANKL. Additionally, we found that silencing Smad4 attenuated the upregulation of miR-155 induced by $TGF{\beta}1$. The results of luciferase reporter experiments and ChIP assays demonstrated that $TGF{\beta}1$ promoted the binding of Smad4 to the miR-155 promoter at a site located in 454 bp from the transcription start site in vivo, further verifying that miR-155 is a transcriptional target of the $TGF{\beta}1/Smad4$ pathway. Subsequently, TRAP staining and qRT-PCR analysis revealed that silencing Smad4 impaired the $TGF{\beta}1$-mediated inhibition on osteoclast differentiation. Finally, we found that miR-155 may target SOCS1 and MITF to suppress osteoclast differentiation. Taken together, we provide the first evidence that $TGF{\beta}1/Smad4$ signaling affects osteoclast differentiation by regulation of miR-155 expression and the use of miR-155 as a potential therapeutic target for osteoclast-related diseases shows great promise.

• 미생물학회지
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• 제40권1호
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• pp.7-11
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• 2004

eIF5B는 단백질합성의 개시 인자로서 Met-$tRNA^{Met}$을 AUG 개시코돈에 전달하고, 리보솜의 두 소단위체 결합을 유도한다. 이 인자의 기능을 연구할 목적으로 eIF5B를 코딩하는 FUN12 유전자의 5'말단 부위를 삭제하는 연구를 수행하였다. 프로모터의 대부분을 삭제한 FUN12를 함유한 pRS효모벡터를 FUN12가 삭제되어 천천히 자라는 돌연변이주 ($fun12{\Delta}g$)에 전달하였을 때 그 표현형을 부분적으로 상보하였다. 위와 같이 제조된 벡터에서 N-말단이 상실된 eIF5B 단백질이 발현되었고, 그 양이 정상 균주에서 발현되는 eIF5B 양의 약 5%에 불과하였다. 이와 같이 부분적으로 성장을 상보한 균주에서 발현된 적은 양의 단백질합성개시 인자 eIF5B는 직접적으로 그 성장을 제한하는 요소로 작용한다. 이러한 균주에서 성장의 제한인자인 eIF5B는 in vitro 에서도 역시 전체 단백질 합성의 활성을 조절하였다.

• Molecules and Cells
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• 제37권1호
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• pp.51-57
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• 2014

NOG1 is a nucleolar GTPase that is critical for 60S ribosome biogenesis. Recently, NOG1 was identified as one of the downstream regulators of target of rapamycin (TOR) in yeast. It is reported that TOR is involved in regulating lifespan and fat storage in Caenorhabditis elegans. Here, we show that the nog1 ortholog (T07A9.9: nog-1) in C. elegans regulates growth, development, lifespan, and fat metabolism. A green fluorescence protein (GFP) promoter assay revealed ubiquitous expression of C. elegans nog-1 from the early embryonic to the adult stage. Furthermore, the GFP-tagged NOG-1 protein is localized to the nucleus, whereas the aberrant NOG-1 protein is concentrated in the nucleolus. Functional studies of NOG-1 in C. elegans further revealed that nog-1 knockdown resulted in smaller broodsize, slower growth, increased life span, and more fat storage. Moreover, nog-1 over-expression resulted in decreased life span. Taken together, our data suggest that nog-1 in C. elegans may be an important player in regulating life span and fat storage via the insulin/IGF pathway.

• Molecules and Cells
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• 제37권1호
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• pp.24-30
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• 2014

Inductive expression of early growth response 1 (Egr-1) in neurons is associated with many forms of neuronal activity. However, only a few Egr-1 target genes are known in the brain. The results of this study demonstrate that Egr-1 knockout (KO) mice display impaired contextual extinction learning and normal fear acquisition relative to wild-type (WT) control animals. Genome-wide microarray experiments revealed 368 differentially expressed genes in the hippocampus of Egr-1 WT exposed to different phases of a fear conditioning paradigm compared to gene expression profiles in the hippocampus of KO mice. Some of genes, such as serotonin receptor 2C (Htr2c), neuropeptide B (Npb), neuronal PAS domain protein 4 (Npas4), NPY receptor Y1 (Npy1r), fatty acid binding protein 7 (Fabp7), and neuropeptide Y (Npy) are known to regulate processing of fearful memories, and promoter analyses demonstrated that several of these genes contained Egr-1 binding sites. This study provides a useful list of potential Egr-1 target genes which may be regulated during fear memory processing.