• Journal of Life Science
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• v.14 no.4
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• pp.716-725
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• 2004

Sox protein family, a transcription factor, has been found in whole animal kingdom, and contains a sequence-specific DNA binding domain called high mobility group domain (HMG). The Sox protein family based on the amino acid sequence of HMG domain was classified into 10 groups. Each group of Sox family shows significant conservation from nematode to human. The HMG domain affect to various developmental cell differentiation through binding to enhancer and regulating other transcription factors. Recently, many molecular biologists focus their research on the illustration of Sox-related disease, evolution and phylogeny. Especially, stem cell research with Sox gene family is indispensable field for understanding of their biological functions. The understanding of Sox genes may contribute to understand their role in human genetic disease and whole animal evolution.

• 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.

• Journal of Microbiology
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• v.35 no.4
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• pp.277-283
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• 1997

Promoters inducible by paraquat, a superocide-generating agent, were isolated from Escherichia coli using a promoter-probing plasmid pRS415 with promoterless lacA gene. Twenty one promoters induced by paraquat were selected and further characterized. From sequence analysis, thirteen of the promoters were mapped to their specific loci on the Escherichia coli chromosome. Several promoters were mapped to the upstream of known genes such as usgl, katG, and mglB, whose relationships with superoxide response have not been previously reported. Other promoters were mapped to the upstream region of unknown open reading frames. Downstream of HC 96 promoter are uncharacterized ORFs whose sequences are homologous to ABC-transporter subunits. Downstream of HC84 promoter is an ORF encoding a transcriptional regulator-like protein, which contains a LysR family-specific HTH (helix-turn-helix) DNA bindign motif. We investigated whether these promoters belong to the soxRS regulon. All promoters except HC96 were found to belong to the soxRS regulon. The HC96 promoter was significantly induced by paraquat in the soxRS deletion mutant strain. The basal transcription level of three promoters (HE43, HC71, HD94) significantly increased at the stationary phase, implying that they are regulated by RpoS. However, paraquat inducibility of all promoters disappeared in the stationary phase, suggesting that SoxRS regulatory system is active only in rapidly growing cells.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.22 no.5
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• pp.487-492
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• 2019

Waardenburg syndrome (WS) type IV is characterized by pigmentary abnormalities, deafness and Hirschsprung's disease. This syndrome can be triggered by dysregulation of the SOX10 gene, which belongs to the SOX (SRY-related high-mobility group-box) family of genes. We discuss the first known case of a SOX10 frameshift mutation variant defined as c.895delC causing WS type IV without Hirschsprung's disease. This female patient of unrelated Kuwaiti parents, who tested negative for cystic fibrosis and Hirschsprung's disease, was born with meconium ileus and malrotation and had multiple surgical complications likely due to chronic intestinal pseudo-obstruction. These complications included small intestinal necrosis requiring resection, development of a spontaneous fistula between the duodenum and jejunum after being left in discontinuity, and short gut syndrome. This case and previously reported cases demonstrate that SOX10 gene sequencing is a consideration in WS patients without aganglionosis but with intestinal dysfunction.

• Molecules and Cells
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• v.22 no.3
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• pp.353-359
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• 2006

The bone morphogenetic protein (BMP) family has been implicated in control of cartilage development. Here, we demonstrate that BMP-2 promotes chondrogenesis by activating p38 mitogen-activated protein kinase (MAPK), which in turn downregulates $Wnt-7a/{\beta}$-catenin signaling responsible for proteasomal degradation of Sox9. Exposure of mesenchymal cells to BMP-2 resulted in upregulation of Sox9 protein and a concomitant decrease in the level of ${\beta}$-catenin protein and Wnt-7a signaling. In agreement with this, the interaction of Sox9 with ${\beta}$-catenin was inhibited in the presence of BMP-2. Inhibition of the p38 MAPK pathway using a dominant negative mutant led to sustained Wnt-7a signaling and decreased Sox9 expression, with consequent inhibition of precartilage condensation and chondrogenic differentiation. Moreover, overexpression of ${\beta}$-catenin caused degradation of Sox9 via the ubiquitin/26S proteasome pathway. Our results collectively indicate that the increase in Sox9 protein resulting from downregulation of ${\beta}$-catenin/Wnt-7a signaling is mediated by p38 MAPK during BMP-2 induced chondrogenesis in chick wing bud mesenchymal cells.

• Journal of Dental Rehabilitation and Applied Science
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• v.40 no.1
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• pp.13-23
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• 2024

Purpose: This aim of this study was to demonstrate growth factors that differentiate human mesenchymal stem cells into chondrocytes and to evaluate cell proliferation enhancement by needle size differences. Materials and Methods: Human mesenchymal stem cells were cultured in chondrogenic medium supplemented with BMP-2, BMP-4, BMP-6, BMP-7, BMP-13, FGF-2, FGF-18, IGF-1, TGF-β1, TGF-β2, TGF-β3 and without growth factors for 14, 21, and 28 days. Then, the expression levels of SOX-5, SOX-6, SOX-9 and FOXO1A were comparatively analyzed. Human mesenchymal stem cells were inoculated into culture dishes using 18, 21, and 26 gauge (G) needles, and cell proliferation was measured after 24, 48, and 72 hours, respectively. Results: In addition to the previously known FGF, IGF-1, and TGFβ1,the BMP family growth factors such as BMP-2, BMP-4, BMP-6, and BMP-7 increased the expression of chondrocyte differentiation genes SOX-5, SOX-6, SOX-9, and FOXO1A. At 48 hours, the 26G group, the smallest needle, showed significant cell proliferation improvement compared to the control group and the 18G group. At 72 hours, the 26G group, the smallest needle, showed significant increase in cell proliferation compared to the control group. Conclusion: Through this study, growth factors with the ability to induce chondrocyte differentiation of human mesenchymal stem cells were investigated, and cell proliferation changes by needle size differences were determined.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.29 no.2
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• pp.62-72
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• 2018

Objectives: The molecular mechanisms underlying attention-deficit hyperactivity disorder (ADHD) remain unclear. Therefore, this study aimed to identify the genetic susceptibility loci for ADHD in Korean children with ADHD. We performed a case-control and a family-based genome-wide association study (GWAS), as well as genome-wide quantitative trait locus (QTL) analyses, for two symptom traits. Methods: A total of 135 subjects (71 cases and 64 controls), for the case-control analysis, and 54 subjects (27 probands and 27 unaffected siblings), for the family-based analysis, were included. Results: The genome-wide QTL analysis identified four single nucleotide polymorphisms (SNPs) (rs7684645 near APELA, rs12538843 near YAE1D1 and POU6F2, rs11074258 near MCTP2, and rs34396552 near CIDEA) that were significantly associated with the number of inattention symptoms in ADHD. These SNPs showed possible association with ADHD in the family-based GWAS, and with hyperactivity-impulsivity in genome-wide QTL analyses. Moreover, association signals in the family-based QTL analysis for the number of inattention symptoms were clustered near genes IL10, IL19, SCL5A9, and SKINTL. Conclusion: We have identified four QTLs with genome-wide significance and several promising candidates that could potentially be associated with ADHD (CXCR4, UPF1, SETD5, NALCN-AS1, ERC1, SOX2-OT, FGFR2, ANO4, and TBL1XR1). Further replication studies with larger sample sizes are needed.

• Development and Reproduction
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• v.12 no.2
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• pp.159-168
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• 2008

Nanog is a newly identified member of the homeobox family of DNA binding transcription factors that functions to maintain the undifferentiated state of stem cells. However, molecular mechanisms underlying the function of Nanog remain largely unknown. To elucidate the regulatory roles of Nanog involved in maintenance of P19 embryonal carcinoma (EC) stem cells, we transfected three small interfering RNA (siRNA) duplexes targeted against different regions of the Nanog gene into P19 cells. The Nanog siRNA-100 duplexes effectively decreased the expression of Nanog up to 30.7% compared to other two Nanog siRNAs, the Nanog siRNA-400 (67.9 %) and -793 (53.0%). When examined by RT-PCR and real-time PCR, the expression of markers for pluripotency such as Fgf4, Oct3/4, Rex1, Sox1 and Yes was downregulated at 48 h after transfection with Nanog siRNA-100. Furthermore, expression of the ectodermal markers, Fgf5 and Isl1 was reduced by Nanog knockdown. By contrast, the expression of other markers for pluripotency such as Cripto, Sox2 and Zfp57 was not affected by Nanog knockdown at this time. On the other hand, the expression of Lif/Stat3 pathway molecules and of the endoderm markers including Dab2, Gata4, Gata6 and the germ cell nuclear factor was not changed by Nanog knockdown. The results of this study demonstrated that the knockdown of Nanog expression by RNA interference in P19 cells was sufficient to modulate the expression of pluripotent markers involved in the self-renewal of EC stem cells. These results provide the valuable information on potential downstream targets of Nanog and add to our understanding of the function of Nanog in P19 EC stem cells.