• Title, Summary, Keyword: S6K1

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Molecular Characterization and Expression Analysis of S6K1 in Cashmere Goats (Capra hircus)

  • Wu, Manlin;Bao, Wenlei;Hao, Xiyan;Zheng, Xu;Wang, Yanfeng;Wang, Zhigang
    • Asian-Australasian Journal of Animal Sciences
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    • v.26 no.8
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    • pp.1057-1064
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    • 2013
  • p70 ribosomal S6 kinase (p70S6K) can integrate nutrient and growth factor signals to promote cell growth and survival. We report our molecular characterization of the complementary DNA (cDNA) that encodes the goat p70S6K gene 40S ribosomal S6 kinase 1 (S6K1) (GenBank accession GU144017) and its 3' noncoding sequence in Inner Mongolia Cashmere goats (Capra hircus). Goat S6K1 cDNA was 2,272 bp and include an open reading frame (ORF) of 1,578 bp, corresponding to a polypeptide of 525 amino acids, and a 694-residue 3' noncoding sequence with a polyadenylation signal at nucleotides 2,218 to 2,223. The relative abundance of S6K1 mRNA was measured by real-time PCR in 6 tissues, and p70S6K expression was examined by immunohistochemistry in heart and testis. The phosphorylation of p70S6K is regulated by mitogen-activated protein kinase (MAPK) signaling in fetal fibroblasts.

Epigenetic role of nuclear S6K1 in early adipogenesis

  • Yi, Sang Ah;Han, Jihoon;Han, Jeung-Whan
    • BMB Reports
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    • v.49 no.8
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    • pp.401-402
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    • 2016
  • S6K1 is a key regulator of cell growth, cell size, and metabolism. Although the role of cytosolic S6K1 in cellular processes is well established, the function of S6K1 in the nucleus remains poorly understood. Our recent study has revealed that S6K1 is translocated into the nucleus upon adipogenic stimulus where it directly binds to and phosphorylates H2B at serine 36. Such phosphorylation promotes EZH2 recruitment and subsequent histone H3K27 trimethylation on the promoter of its target genes including Wnt6, Wnt10a, and Wnt10b, leading to repression of their expression. S6K1-mediated suppression of Wnt genes facilitates adipogenic differentiation through the expression of adipogenic transcription factors PPARγ and Cebpa. White adipose tissues from S6K1-deficient mice consistently exhibit marked reduction in H2BS36 phosphorylation (H2BS36p) and H3K27 trimethylation (H3K27me3), leading to enhanced expression of Wnt genes. In addition, expression levels of H2BS36p and H3K27me3 are highly elevated in white adipose tissues from mice fed on high-fat diet or from obese humans. These findings describe a novel role of S6K1 as a transcriptional regulator controlling an epigenetic network initiated by phosphorylation of H2B and trimethylation of H3, thus shutting off Wnt gene expression in early adipogenesis.

Experimental Proof for Symmetric Ramsey Numbers (대칭 램지 수의 실험적 증명)

  • Lee, Sang-Un
    • Journal of the Korea Society of Computer and Information
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    • v.20 no.3
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    • pp.69-74
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    • 2015
  • This paper offers solutions to unresolved $43{\leq}R(5,5){\leq}49$ and $102{\leq}R(6,6){\leq}165$ problems of Ramsey's number. The Ramsey's number R(s,t) of a complete graph $k_n$ dictates that n-1 number of incidental edges of a arbitrary vertex ${\upsilon}$ is dichotomized into two colors: (n-1)/2=R and (n-1)/2=B. Therefore, if one introduces the concept of distance to the vertex ${\upsilon}$, one may construct a partite graph $K_n=K_L+{\upsilon}+K_R$, to satisfy (n-1)/2=R of {$K_L,{\upsilon}$} and (n-1)/2=B of {${\upsilon},K_R$}. Subsequently, given that $K_L$ forms the color R of $K_{s-1)$, $K_S$ is attainable. Likewise, given that $K_R$ forms the color B of $K_{t-1}$, $K_t$ is obtained. By following the above-mentioned steps, $R(s,t)=K_n$ was obtained, satisfying necessary and sufficient conditions where, for $K_L$ and $K_R$, the maximum distance should be even and incidental edges of all vertices should be equal are satisfied. This paper accordingly proves R(5,5)=43 and R(6,6)=91.

Rates and Mechanism of the Reaction of Aquaoxomolybdenum(IV) Trimer with Thiocyanate (아쿠아옥소몰리브덴(IV) 삼합체 착물과 티오시안산이온과의 반응에 대한 속도와 메카니즘)

  • Chang-Su Kim;Joong-Ho Lee
    • Journal of the Korean Chemical Society
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    • v.31 no.6
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    • pp.527-533
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    • 1987
  • Kinetic studies on the complexing of aquamolybdenum(Ⅳ) trimer with thiocyanate have been carried out using the spectrophotometric method. The observed rate constant, $k_{obsd}$ is given by $k_{obsd}\;=\;{k_O + k_H[H^+]^2}(SCN^-) + k_r$. At 25$^{\circ}$C and ionic strength of 2.30 the values of $k_f$ and $k_r$ are $(3.78 {\pm} 0.61) {\times} 10^{-4}M^{-1}s^{-1}$ and $(6.93 {\pm} 2.39) {\times} 10^{-4}s^{-1}$, respectively. Activation parameters are ${\Delta}H^* = 50.71{\pm}6.91 kJmol^{-1}$ and ${\Delta}S^* = -121.65JK^{-1}mol^{-1}$. The mechanism is proposed and discussed.

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Constitutive Activation of $p70^{S6k}$ in Cancer Cells

  • Kwon, Hyoung-Keun;Bae, Gyu-Un;Yoon, Jong-Woo;Kim, Yong-Kee;Lee, Hoi-Young;Lee, Hyang-Woo;Han, Jeung-Whan
    • Archives of Pharmacal Research
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    • v.25 no.5
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    • pp.685-690
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    • 2002
  • The mitogen-stimulated serine/threonine kinase $p70^{S6k}$ plays an important role in the progression of cells from $G_0/G$_1$$ to S phase of the cell cycle by translational up-regulation of a family of mRNA transcripts family of mRNA transcripts which contain polypyrimidine tract at their 5 transcriptional start site. Here, we report that $p70^{S6k}$ was constitutively phosphorylated and activated to various degrees in serum-deprived AGS, A2058, HT-1376, MG63, MCF7, MDA-MB-435S, MDA-MB-231 and MB-157. Rapamycin treatment induced a significant dephosphorylation and inactivation of $p70^{S6k}$ in all cancer cell lines, while wortmannin, a specific inhibitor of PI3-K, caused a mild dephosphorylation of $p70^{S6k}$ in AGS, MDA-MB-435S and MB-157. In addition, SQ20006, methylxanthine phosphodiesterase inhibitor, reduced the phosphorylation of $p70^{S6k}$ in all cancer cells tested. Consistent with inhibitory effect of rapamycin on $p70^{S6k}$ activity, rapamycin inhibited [$^3H$]-thymidine incorporation and increased the number of cells at $G_{0}G_{1}$ phase. Furthermore, these inhibitory effects were accompanied by the decrease in growth of cancer cells. Taken together, the results indicate that the antiproliferative activity of rapamycin might be attributed to cell cycle arrest at $G_{0}G_{1}$ phase in human cancer cells through the inhibition of constitutively activated $p70^{S6k}$ of cancer cells and suggest $p70^{S6k}$ as a potential target for therapeutic strategies aimed at preventing or inhibiting tumor growth.

Fermented ginseng extract, BST204, disturbs adipogenesis of mesenchymal stem cells through inhibition of S6 kinase 1 signaling

  • Yi, Sang Ah;Lee, Jieun;Park, Sun Kyu;Kim, Jeom Yong;Park, Jong Woo;Lee, Min Gyu;Nam, Ki Hong;Park, Jee Hun;Oh, Hwamok;Kim, Saetbyul;Han, Jihoon;Kim, Bo Kyung;Jo, Dong-Gyu;Han, Jeung-Whan
    • Journal of Ginseng Research
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    • v.44 no.1
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    • pp.58-66
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    • 2020
  • Background: The biological and pharmacological effects of BST204, a fermented ginseng extract, have been reported in various disease conditions. However, its molecular action in metabolic disease remains poorly understood. In this study, we identified the antiadipogenic activity of BST204 resulting from its inhibition of the S6 kinase 1 (S6K1) signaling pathway. Methods: The inhibitory effects of BST204 on S6K1 signaling were investigated by immunoblot, nuclear fractionation, immunoprecipitation analyses. The antiadipogenic effect of BST204 was evaluated by measuring mRNA levels of adipogenic genes and by chromatin immunoprecipitation and quantitative real-time polymerase chain reaction analysis. Results: Treatment with BST204 inhibited activation and nuclear translocation of S6K1, further decreasing the interaction between S6K1 and histone H2B in 10T1/2 mesenchymal stem cells. Subsequently, phosphorylation of H2B at serine 36 (H2BS36p) by S6K1 was reduced by BST204, inducing an increase in the mRNA expression of Wnt6, Wnt10a, and Wnt10b, which disturbed adipogenic differentiation and promoted myogenic and early osteogenic gene expression. Consistently, BST204 treatment during adipogenic commitment suppressed the expression of adipogenic marker genes and lipid drop formation. Conclusion: Our results indicate that BST204 blocks adipogenesis of mesenchymal stem cells through the inhibition of S6K1-mediated histone phosphorylation. This study suggests the potential therapeutic strategy using BST204 to combat obesity and musculoskeletal diseases.

Kinetic Study of Proton Exchange between Al($H_2O$)$_6^{3+}$ Ion and Bulk Water Molecules (Ⅰ) (Al($H_2O$)$_6^{3+}$ 이온과 물 용매 분자 사이에서의 수소 이온 교환의 반응속도론적 연구 (Ⅰ))

  • Moon-Hwan Cho;Jin-Ho Kim;Chang-Ju Yoon
    • Journal of the Korean Chemical Society
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    • v.32 no.5
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    • pp.436-442
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    • 1988
  • The $^1H-nmr$ lineshapes of $H_2O$ in the solution containing $Al^{3+}$ ion have been measured as a function of temperature and $H^+$-ion concentration. Above [$H^+$] = 0.06, the lineshape were analyzed by the uncoupled two-site exchange model. From the proton exchange rate between hexaaquaaluminium ion and bulk water as a function of H-ion concentration. These kinetic data could be fitted to a following linear rate law; that is; 1/${\tau}$ = k$_1$/12 + $k_2$[$H^+$]/6. The following proton exchange parameters were obtained; $k_1^{298}$ = 38.5s$^{-1}$ ${\{Delta}H_1^{\neq}$ = $42.9kJ mole^{-1}$ ${\{Delta}S_1^{\neq}$ = -48.6J $mole^{-1}K^{-1}$ $k_2^{298}$ = $172s^{-1}mole^{-1}$ ${\{Delta}H_2^{\neq}$ = 27.8kJ $mole^{-1}$ ${\{Delta}S_2^{\neq}$ = -90.3J $mole^{-1}K^{-1}$ These activation parameters are indicating an associative interchange, Ia, mechanism for the acid-hydrolysis of hexaaquaaluminium ion and the proton exchange between the hydration spheres of $Al^{3+}$ and $H^+$.

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2K/8K FFT Implementation with Stratix EP1S25F672C6 FPGA for DVB (DVB용 2K/8K FFT의 Stratix EP1S25F672C6 FPGA 구현)

  • Min, Jong-Kyun;Cho, Joong-Hwee
    • Journal of the Institute of Electronics Engineers of Korea SD
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    • v.44 no.8
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    • pp.60-64
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    • 2007
  • In this paper, we designed FFT for European DTV and implemented system with Stratix EP1S25F672C6 FPGA At the implemented FFT, we used SIC architecture. SIC architecture is composed of algorithm-specific processing element, RAM memory, registers, and a central or distributed control unit. Designed FFT was acceptable either 2K or 8K point FFT processing, and is selectable guard interval such as 1/4, 1/8, 1/16, 1/32. Consequently, it was suitable for the standard of DVB-T(Digital Terrestrial Video Transmission System) specification. It resulted in 12% of total logic gate and 53% of total memory bit in Stratix device.

Heteroexpression and Functional Characterization of Glucose 6-Phosphate Dehydrogenase from Industrial Aspergillus oryzae

  • Guo, Hongwei;Han, Jinyao;Wu, Jingjing;Chen, Hongwen
    • Journal of Microbiology and Biotechnology
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    • v.29 no.4
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    • pp.577-586
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    • 2019
  • The engineered Aspergillus oryzae has a high NADPH demand for xylose utilization and overproduction of target metabolites. Glucose-6-phosphate dehydrogenase (G6PDH, E.C. 1.1.1.49) is one of two key enzymes in the oxidative part of the pentose phosphate pathway, and is also the main enzyme involved in NADPH regeneration. The open reading frame and cDNA of the putative A. oryzae G6PDH (AoG6PDH) were obtained, followed by heterogeneous expression in Escherichia coli and purification as a his6-tagged protein. The purified protein was characterized to be in possession of G6PDH activity with a molecular mass of 118.0 kDa. The enzyme displayed maximal activity at pH 7.5 and the optimal temperature was $50^{\circ}C$. This enzyme also had a half-life of 33.3 min at $40^{\circ}C$. Kinetics assay showed that AoG6PDH was strictly dependent on $NADP^+$ ($K_m=6.3{\mu}M$, $k_{cat}=1000.0s^{-1}$, $k_{cat}/K_m=158.7s^{-1}{\cdot}{\mu}M^{-1}$) as cofactor. The $K_m$ and $k_{cat}/K_m$ values of glucose-6-phosphate were $109.7s^{-1}{\cdot}{\mu}M^{-1}$ and $9.1s^{-1}{\cdot}{\mu}M^{-1}$ respectively. Initial velocity and product inhibition analyses indicated the catalytic reaction followed a two-substrate, steady-state, ordered BiBi mechanism, where $NADP^+$ was the first substrate bound to the enzyme and NADPH was the second product released from the catalytic complex. The established kinetic model could be applied in further regulation of the pentose phosphate pathway and NADPH regeneration of A. oryzae to improve its xylose utilization and yields of valued metabolites.

Magnetoresistance Effects in Cr5S6 Single Crystal (Cr5S6 단결정의 자기저항 효과)

  • Lee, Kyung-Dong;Song, Ki-Myung;Hur, Nam-Jung
    • Journal of the Korean Magnetics Society
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    • v.20 no.6
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    • pp.207-211
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    • 2010
  • We have investigated the magnetoresistance effect in $Cr_5S_6$ single crystals prepared by vapor transport method. Room temperature X-ray diffraction (XRD) study reveals the phase formation of the single crystals with trigonal crystal structure. The magnetization was measured as a function of temperature (5 K~400 K) and applied magnetic field (0.1 T and 5 T). The magnetization curve as a function of temperature reveals the two transition states of $Cr_5S_6$: one from antiferromagnetic to ferrimagnetic state at ~150 K and the other from ferrimagnetic to paramagnetic state at ~300 K. Temperature dependent resistivity at 0 T and 5 T magnetic field shows the metallic behavior, showing the transition from antiferromagnetic to ferrimagnetic state at ~150 K. Magnetic field dependence of magnetization was measured at four fixed temperatures viz. 100 K, 150 K, 200 K, and 300 K. It is observed that at 200 K and 300 K it shows well M-H hysteresis behavior, whereas at 100 K and 150 K it shows non-hysteretic nature. A negative magnetoresistance (MR) of -2% is observed at 5 T for $Cr_5S_6$ single crystal at 150 K, near the antiferromagnetic transition temperature.