• Title/Summary/Keyword: SOX-2

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

  • Seok, Hyun-Jeong;Kim, Young-Eun;Park, Jeong-A;Lee, Young-Hee
    • Development and Reproduction
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    • v.14 no.2
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    • pp.123-129
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    • 2010
  • Embryonic stem (ES) cells can self-renew maintaining the undifferentiated state. Self-renewal requires many factors such as OCT4, SOX2, and NANOG. It is previously known that OCT4 and SOX2 can bind to NANOG promoter and support Nanog gene expression in mouse ES cells by the detailed studies using the mouse Nanog promoter. Here, we constructed serial deletion mutant promoter-reporter constructs to investigate the human Nanog gene promoter in detail. The highest promoter activity was obtained in the 0.6 kb (-253/+365) promoter-reporter construct which includes the binding sites of OCT4 and SOX2. To further confirm contribution of OCT4 and SOX2 in Nanog gene expression, we introduced site- directed mutation(s) in the OCT4 and/or SOX2 binding sites of the human Nanog promoter 0.6 kb (-253/+365) and checked the influence of the mutation on the promoter activity using human EC cell line NCCIT. Mutation either in OCT4 binding site or SOX2 binding site significantly reduced the activity of Nanog promoter which directly confirmed that OCT4 and SOX2 binding is essential in human Nanog gene expression.

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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    • v.47 no.4
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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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    • v.24 no.3
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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.

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

  • 허은혜;최주연;장경희;김인경;임향숙
    • Korean Journal of Microbiology
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    • v.38 no.3
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    • pp.153-161
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    • 2002
  • Sox4, a transcription factor, consists of three functional domains: an HMG-box domain as a DNA binding domain, serine rich region as a transactivation domain and glycine rich region (GRR), an unknown functional domain. Although Sox4 is known to be functionally involved in heart, B-cell and reproductive system development, its physiological function remains to be elucidated. We used pGEX expression system to develop a simple and rapid method for purifying Sox4 protein in suitable forms for biochemical studies of their functions. Unexpectedly, we observed that full-length Sox4 appears to be protease-sensitive during expression and purification in E. coli. To map the protease-sensitive site in Sox4, we generated various constructs with each of functional domains of Sox4 and purified as the GST-Sox4 fusion proteins using glutathione beads. We found that the specific cleavage site for the proteolytic enzyme, which exists in E. coli, is localized within the novel GRR of Sox4. Our study suggest that the GRR of Sox4 may a target for the cellular protease action and this cleavage in the GRR may be involved in regulating physiological function of Sox4. Additionally, our study may provide a useful method for investigating the proteolytic cleavage of the target molecule in E. coli.

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

  • 이용근;이동수;백선영
    • Journal of Korean Society for Atmospheric Environment
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    • v.11 no.4
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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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    • v.41 no.6
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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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    • v.49 no.6
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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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    • v.2 no.2
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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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    • v.15 no.13
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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.

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

  • Yoon, Se Young;Hong, Min Eui;Sim, Sang Jun
    • Journal of Hydrogen and New Energy
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    • v.24 no.3
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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.