• Title/Summary/Keyword: SOX-2

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OCT4와 SOX2에 의한 인간 Nanog 유전자의 전사 조절 (Transcriptional Regulation of Human Nanog Gene by OCT4 and SOX2)

  • 석현정;김영은;박정아;이영희
    • 한국발생생물학회지:발생과생식
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    • 제14권2호
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    • pp.123-129
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    • 2010
  • 배아 줄기세포는 미분화상태에서 자가 재생을 유지할 수 있다. 자가 재생은 OCT4, SOX2와 NANOG와 같은 많은 인자들이 작용한다. 생쥐 배아 줄기세포에서 OCT4와 SOX2가 Nanog 프로모터에 결합하여 Nanog 유전자의 발현을 촉진한다는 사실은 생쥐 promoter에 관한 정밀분석으로 알려져 있다. 본 연구에서는 인간 Nanog promoter를 정밀 분석하기 위해 연속적인 결손 돌연변이를 가진 promoter-reporter construct를 제조하였다. Promoter의 최대 활성은 0.6 kb(-253/+365) promoter-reporter construct에서 발견되었으며, 이 construct에는 OCT4 및 SOX2의 결합부위가 포함된다. OCT4와 SOX2의 기여도를 확인하기 위하여 OCT4 및 SOX2의 결합부위에 자리 특이적 돌연변이를 유도하고 promoter 활성에 미치는 영향을 조사한 결과, OCT4나 SOX2 어느 한 군데라도 돌연변이가 존재하면 promoter 활성이 현저히 저해되었다. 본 연구 결과를 통해 인간 Nanog 유전자 발현에 있어 OCT4 및 SOX2가 필수적임을 직접적으로 확인할 수 있었다.

Cyclic AMP response element binding (CREB) protein acts as a positive regulator of SOX3 gene expression in NT2/D1 cells

  • Kovacevic-Grujicic, Natasa;Mojsin, Marija;Popovic, Jelena;Petrovic, Isidora;Topalovic, Vladanka;Stevanovic, Milena
    • BMB Reports
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    • 제47권4호
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    • pp.197-202
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    • 2014
  • SOX3 is one of the earliest neural markers in vertebrates, playing the role in specifying neuronal fate. In this study we have established first functional link between CREB and human SOX3 gene which both have important roles in the nervous system throughout development and in the adulthood. Here we demonstrate both in vitro and in vivo that CREB binds to CRE half-site located -195 to -191 within the human SOX3 promoter. Overexpression studies with CREB or its dominant-negative inhibitor A-CREB indicate that this transcription factor acts as a positive regulator of basal SOX3 gene expression in NT2/D1 cells. This is further confirmed by mutational analysis where mutation of CREB binding site results in reduction of SOX3 promoter activity. Our results point at CREB as a positive regulator of SOX3 gene transcription in NT2/D1 cells, while its contribution to RA induction of SOX3 promoter is not prominent.

Overexpression of SOX15 Inhibits Proliferation of NT2/D1 Cells Derived from a Testicular Embryonal Cell Carcinoma

  • Yan, Hong-Tao;Shinka, Toshikatsu;Sato, Youichi;Yang, Xin-Jun;Chen, Gang;Sakamoto, Kozue;Kinoshita, Keigo;Aburatani, Hiroyuki;Nakahori, Yutaka
    • Molecules and Cells
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    • 제24권3호
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    • pp.323-328
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    • 2007
  • SOX (Sry-related HMG box) family proteins, which have an evolutionarily conserved DNA binding domain, have crucial roles in cell differentiation. However, their target genes remain enigmatic. Some members of the SOX family may have roles in regulation of cell proliferation. We established stable NT2/D1 cell lines overexpressing SOX15 (SOX15-NT2/D1), and a modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that the SOX15-NT2/D1 cells exhibited significantly slower growth than the controls. Flow cytometry analysis revealed that an increased fraction of the SOX15-NT2/D1 cells were in G1-G0. In addition, a microarray analysis identified 26 genes that were up-regulated in the SOX15-NT2/D1 cells, but none that were down-regulated genes. Among the up-regulated genes, IGFBP5, S100A4, ID2, FABP5, MTSS1, PDCD4 have been shown to be related to cell proliferation and/or the cell cycle.

전사활성 인자인 Sox4의 단백질 분해효소에 의한 표적 부위에 관한 연구 (A Novel Glycine-Rich Region in Sox4 is a Target for the Proteolytic Cleavage in E. coli)

  • 허은혜;최주연;장경희;김인경;임향숙
    • 미생물학회지
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    • 제38권3호
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    • pp.153-161
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    • 2002
  • Sox4는 DNA 결합 도메인인 HMG-box와 전사 활성 도메인인 serine rich region (SRR)과 아직 그 기능이 알려져 있지 않은 glycine rich region (GRR)등의 세 개의 기능 도메인을 가지는 전사인자이다. 전사인자인 Sox4는 생체 내 초기 분화 시 중요한 역할을 하는 유전자로 알려져 있으나 여전히 그 정확한 생리적 기능 및 세포 내에서 이 유전자 산물이 전사 활성 에 어떻게 관여하는지 그 정확한 기전은 잘 밝혀져 있지 않다. 이에 본 연구에서는 Sox4의 생리적 기능을 이해하고 세포 내에서 Sox4의 기능 연구에 유용하게 사용할 수 있는 항체를 제조하기 위해 Sox4를 대장균에서 발현, 정제하였다. 모든 기능 도메인을 다 포함하는 Sox4는 대장균에서 발현 시 대부분 절단되는 양상을 나타내었다. Sox4의 각 도메인을 대장균에서 GST-융합 단백질로 발현, 정제하여 그 발현 양상을 비교해 본 바 N-말단을 제거한 Sox4 ($\Delta$HMG)의 경우 67 kDa 크기의 단백질이 생성되므로 이 단백질을 항원으로 이용하여 Sox4의 GRR에 특이적으로 반응하는 항체를 제조하였다. 또한, 67 kDa 크기의 단백질 외에 34 kDa 크기에서 GST-융합 단백질이 관찰되었다. 이 밴드는 Sox4 (GRR)를 발현, 정제시에도 관찰되는 동일한 크기의 밴드이며 thrombin과의 반응을 통해 7 kDa 크기로 절단되는 Sox4 밴드이다. 그러므로 이 들 결과로부터 GRR 내에 단백질 분해효소의 표적 부위가 존재함을 확인할 수 있었다. 본 연구결과는 아직 그 기능이 밝혀져 있는 않은 Sox4의 새로운 도메인인 GRR이 단백질 분해 효소의 표적 부위로 작용하여 Sox4의 안정성을 조절함으로써 Sox4의 활성에 중요한 역할을 수행할 수 있다는 가능성을 제시하고 있다.은 억제 회복 효과는 $Mg^{2+}$에 의한 리보자임의 td intron 구조적 안정성에 기인하는 것으로 추정된다.력이 뛰어난(adaptable) 인간적 요구사항을 충족시켜야 한다. 셋째, 다이내믹 시미트리는 역(逆, reciprocity)의 원리와 보상(補賞, complement)의 원리를 제 1의 구성원리로 하며 공간에서 서로에 대한 역과 공통성(common property)을 갖고 자기유사를 지닐 때 연속체(continuum)를 손상하지 않고 전체공간을 유기체적으로 분절한다.같은 pattern 이었다. 그러나 JR89주에서는 280kb 가 나타나지 않아 다른 분리균주와 구분되었다.과 밀가루국(麴) 사이에 차(差)가 별(別)로 없었다.果)에서 총지질(總脂質)을 구성(構咸)하는 지방산(脂肪酸) 조성(組成)은 $C_{18:2}$산(酸), $C_{16:0}$산(酸)의 순(順)으로 그 함량(含最)이 맞은데 비(比)하여 각획분(各劃分)의 지질(脂質)을 구성(構成)하는 지방산(脂肪酸) 조성(組成)은 $C_{16:0}$산(酸), $C_{18:2}$산(酸)의 순(順)으로 그 함량(含量)이 많은 것으로 나타났으며 동결건조후(凍結乾燥後) 저장(貯藏)하는 동안에$C_{18:2}$산(酸), $C_{18:3}$산(酸)의 함량(含量)이 계속(繼續) 감소(減少)하고 있었다. 5. 4-monomethylsterol fraction에는 cycloartenol(20.6%)이 비교적(比較的) 높은 함량(含量)으로 함유(含有)되어 있었고, 그 외(外) cyclolaudenol, cycloeucalenol 및 citrostadienol 등이 함유(含有)되어 있었다. 6. 4-desmethylsterol fraction에

확산포집-이온크로마토그래프법을 이용한 대기중 SOx의 자동정량 (Automated Determination of SOx in Air by Diffusion Scrubber-lon Chromatography)

  • 이용근;이동수;백선영
    • 한국대기환경학회지
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    • 제11권4호
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    • pp.307-313
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    • 1995
  • An automatic method is developed for the determination of SOx in atmosphere. The method involves SOx sampling in diffusion scrubber followed by ion chromatographic analysis. Filtered air is withdrawn at 1.8.ell./min through a diffusion scrubber of which inner tube is made of PTFE(Gore-tex) membrane tubing. 1mM $H_{2}$ $O_{2}$ is used as absorbing solution so that SOx is oxidized to S $O_{4}$$^{2-}$. The scrubbered solution is automatically injected into ion chromatograhpy eith conductivity detection for sulphate determination. Replacement of commonly used polyproplene membrane with PTFE gives several merits such as easy preparation of diffusion scrubber, better collection efficiency. No measurable memory effect is experienced, and this isin contrast to previous work for ammonia. Detection limit of this method defined by three times standard deviation is 0.56ppbv. The precision is 0.4% RSD at SOx concentration of 7.3ppbv Results for Seoulatmosphere ate presented.

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TNF-α-Induced SOX5 Upregulation Is Involved in the Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells Through KLF4 Signal Pathway

  • Xu, Lijun;Zheng, Lili;Wang, Zhifang;Li, Chong;Li, Shan;Xia, Xuedi;Zhang, Pengyan;Li, Li;Zhang, Lixia
    • Molecules and Cells
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    • 제41권6호
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    • pp.575-581
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    • 2018
  • Postmenopausal osteoporosis (PMOP) is a common systemic skeletal disease characterized by reduced bone mass and microarchitecture deterioration. Although differentially expressed SOX5 has been found in bone marrow from ovariectomized mice, its role in osteogenic differentiation in human mesenchymal stem cells (hMSCs) from bone marrow in PMOP remains unknown. In this study, we investigated the biological function of SOX5 and explore its molecular mechanism in hMSCs from patients with PMOP. Our findings showed that the mRNA and protein expression levels of SOX5 were upregulated in hMSCs isolated from bone marrow samples of PMOP patients. We also found that SOX5 overexpression decreased the alkaline phosphatase (ALP) activity and the gene expression of osteoblast markers including Collagen I, Runx2 and Osterix, which were increased by SOX5 knockdown using RNA interference. Furthermore, $TNF-{\alpha}$ notably upregulated the SOX5 mRNA expression level, and SOX5 knockdown reversed the effect of $TNF-{\alpha}$ on osteogenic differentiation of hMSCs. In addition, SOX5 overexpression increased Kruppel-like factor 4 (KLF4) gene expression, which was decreased by SOX5 silencing. KLF4 knockdown abrogated the suppressive effect of SOX5 overexpression on osteogenic differentiation of hMSCs. Taken together, our results indicated that $TNF-{\alpha}$-induced SOX5 upregulation inhibited osteogenic differentiation of hMSCs through KLF4 signal pathway, suggesting that SOX5 might be a novel therapeutic target for PMOP treatment.

GATA4 negatively regulates bone sialoprotein expression in osteoblasts

  • Song, Insun;Jeong, Byung-chul;Choi, Yong Jun;Chung, Yoon-Sok;Kim, Nacksung
    • BMB Reports
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    • 제49권6호
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    • pp.343-348
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    • 2016
  • GATA4 has been reported to act as a negative regulator in osteoblast differentiation by inhibiting the Dlx5 transactivation of Runx2 via the attenuation of the binding ability of Dlx5 to the Runx2 promoter region. Here, we determine the role of GATA4 in the regulation of bone sialoprotein (Bsp) in osteoblasts. We observed that the overexpression of Runx2 or Sox9 induced the Bsp expression in osteoblastic cells. Silencing GATA4 further enhanced the Runx2- and Sox9-mediated Bsp promoter activity, whereas GATA4 overexpression down-regulated Bsp promoter activity mediated by Runx2 and Sox9. GATA4 also interacted with Runx2 and Sox9, by attenuating the binding ability of Runx2 and Sox9 to the Bsp promoter region. Our data suggest that GATA4 acts as a negative regulator of Bsp expression in osteoblasts.

The Effects of SOX and Internal Control Weaknesses on the Relation between the Real Earnings Management and Audit Fees

  • Sohn, Byungcherl Charlie;Shim, Hoshik
    • Asia Pacific Journal of Business Review
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    • 제2권2호
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    • pp.17-44
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    • 2018
  • This study investigates whether the positive relation between the real earnings management (REM) and audit fees reported by Choi et al. (2016) differs before and after the Sarbanes-Oxley Act (SOX), and varies cross-sectionally depending on the existence of internal control problems. Using a large sample of U.S. firms, we find that the positive relation between REM and audit fees is stronger than the same relation between AEM and audit fees in the post-SOX period, whereas the opposite is true in the pre-SOX period. We also find that the positive relation between REM and audit fees is intensified for firms with material internal control weaknesses.

Clinical and Prognostic Significance of SOX11 in Breast Cancer

  • Liu, Dao-Tong;Peng-Zhao, Peng-Zhao;Han, Jing-Yan;Lin, Fan-Zhong;Bu, Xian-Min;Xu, Qing-Xia
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권13호
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    • pp.5483-5486
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    • 2014
  • Recently, the transcription factor SOX11 has gained extensive attention as a diagnostic marker in a series of cancers. However, to date, the possible roles of SOX11 in breast cancer has not been investigated. In this study, immunohistochemical staining for SOX11 was performed for 116 cases of breast cancer. Nuclear SOX11 was observed in 42 (36.2%) and cytoplasmic SOX11 in 52 (44.8%) of breast cancer samples. Moreover, high expression of cytoplasmic and nuclear SOX11 was associated with clinicopathological factors, including earlier tumor grade, absence of lymph node metastasis and smaller tumor size. Kaplan-Meier survival curves demonstrated high nuclear SOX11 expression to be associated with more prolonged overall survival than those with low expression and it could be an independent predictor of survival for breast cancer patients. It is worthwhile to note that cytoplasmic SOX11 was not correlated with prognosis of breast cancer patients. These data suggest the possibility that nuclear SOX11 could be as a potential target for breast cancer therapy.

광배양 시스템에서 NOx 및 SOx의 배지 pH와 미세조류 생장에 미치는 영향 (Effects of NOx and SOx on the Medium pH and microalgal growth in photo-culture system)

  • 윤세영;홍민의;심상준
    • 한국수소및신에너지학회논문집
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    • 제24권3호
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    • pp.255-263
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    • 2013
  • Carbon dioxide reduction technologies using photosynthetic microorganism were suggested to overcome environmental destruction caused by $CO_2$ in flue gases from power plant and other industries. However, there are many toxic constituents in flue gas including CO, NOx, SOx. Continuous and Excessive supply of these noxious gases to cells will leads to inhibition of microalgal growth along with partial cell death. In this study, we tested the noxious effect of SOx and NOx on the pH and microalgal growth under photoautotrophic culture in three microalgae of Neochloris oleoabundans, Chlorella vulgaris and Haematococcus pluvialis. As a result, SOx concentration more than 50 ppm led to the rapid reduction of pH, thereby inhibiting of the growth in Neochloris oleoabundans and Chlorella vulgaris. NOx concentration more the 100 ppm reduced the exponential growth of N. oleoabundans and C. vulgaris. And H. pluvialis exhibited low sensitivity to SOx and NOx. Consequently, the three microalgae of N. oleabundas, C. vulagaris and H. pluvialis showed the normal vegetative growth in 25 ppm of NOx and SOx. Above all, H. pluvialis was useful for the $CO_2$ sequestration of the flue gas including high concentrations of NOx and SOx.