S6K1 Phosphorylation of H2B Mediates EZH2 Trimethylation of H3: A Determinant of Early Adipogenesis

Yi, S.,Um, S.,Lee, J.,Yoo, J.,Bang, S.,Park, E.,Lee, M.,Nam, K.,Jeon, Y.,Park, J.,You, J.,Lee, S.J.,Bae, G.U.,Rhie, J.,Kozma, Sara C.,Thomas, G.,Han, J.W. Cell Press 2016 Molecular Cell Vol.62 No.3

S6K1 has been implicated in a number of key metabolic responses, which contribute to obesity. Critical among these is the control of a transcriptional program required for the commitment of mesenchymal stem cells to the adipocytic lineage. However, in contrast to its role in the cytosol, the functions and targets of nuclear S6K1 are unknown. Here, we show that adipogenic stimuli trigger nuclear translocation of S6K1, leading to H2BS36 phosphorylation and recruitment of EZH2 to H3, which mediates H3K27 trimethylation. This blocks Wnt gene expression, inducing the upregulation of PPARγ and Cebpa and driving increased adipogenesis. Consistent with this finding, white adipose tissue from S6K1-deficient mice exhibits no detectable H2BS36 phosphorylation or H3K27 trimethylation, whereas both responses are highly elevated in obese humans or in mice fed a high-fat diet. These findings define an S6K1-dependent mechanism in early adipogenesis, contributing to the promotion of obesity.

1H NMR Measurements of the Phase Transition of (NH₄)₃H(SO₄)₂ Single Crystals

S. H. Choi,Moohee Lee,Ae Ran Lim,K. S. Han,S. K. Kwon,S. K. Nam 한국물리학회 2008 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.52 No.2

$^1$H nuclear magnetic resonance (NMR) experiments have been performed in the temperature range of 30 -- 300 K at 7 T to investigate the phase-dependent nature of the dynamic network of hydrogen bonds in a ((NH₄)₃H(SO₄)₂ single crystal. The crystal has six phases, which are ferroelectric, antiferroelectric, incommensurate, antiferroelectric, ferroelastic, and superionic with the respective transition temperatures of 63, 133, 139, 256 and 413 K. The spin-lattice relaxation time, T₁, of ¹H NMR is similar for the ammonium protons and the hydrogen-bond protons over the entire range of experimental temperatures. The T₁, of ¹H NMR gradually decreases down to 120 K and starts to steeply increase below 100 K. Then, the T₁ shows an abrupt decrease below 68 K with a sharp minimum at 63 K, where the ferroelectric transition occurs. The ¹H NMR spectrum shifts to the high-frequency side at temperatures below 63 K due to the ferroelectric phase transition. This behavior of the T₁ and the spectrum confirms a dramatic change in the dynamics of hydrogen bonds associated with the ferroelectric phase transition at 63 K. $^1$H nuclear magnetic resonance (NMR) experiments have been performed in the temperature range of 30 -- 300 K at 7 T to investigate the phase-dependent nature of the dynamic network of hydrogen bonds in a ((NH₄)₃H(SO₄)₂ single crystal. The crystal has six phases, which are ferroelectric, antiferroelectric, incommensurate, antiferroelectric, ferroelastic, and superionic with the respective transition temperatures of 63, 133, 139, 256 and 413 K. The spin-lattice relaxation time, T₁, of ¹H NMR is similar for the ammonium protons and the hydrogen-bond protons over the entire range of experimental temperatures. The T₁, of ¹H NMR gradually decreases down to 120 K and starts to steeply increase below 100 K. Then, the T₁ shows an abrupt decrease below 68 K with a sharp minimum at 63 K, where the ferroelectric transition occurs. The ¹H NMR spectrum shifts to the high-frequency side at temperatures below 63 K due to the ferroelectric phase transition. This behavior of the T₁ and the spectrum confirms a dramatic change in the dynamics of hydrogen bonds associated with the ferroelectric phase transition at 63 K.

Facile synthesis of an IRMOF-3 membrane on porous Al₂O₃ substrate via a sonochemical route

Lee, Y.R.,Cho, S.M.,Ahn, W.S.,Lee, C.H.,Lee, K.H.,Cho, W.S. Elsevier 2015 Microporous and mesoporous materials Vol.213 No.-

A densely-packed IRMOF-3 membrane (S-IRMOF-3(Mem)), ~55 μm in thickness, on an Al<SUB>2</SUB>O<SUB>3</SUB> disc support was prepared via a sonochemical synthesis route, and the optimal fabrication conditions were established. Bare IRMOF-3 particles (S-IRMOF-3(p)) were synthesized independently to analyze the contribution of the Al<SUB>2</SUB>O<SUB>3</SUB> support. The overall physicochemical properties of the IRMOF-3 products produced via the sonochemical route were superior to those prepared by microwave heating. The IRMOF-3 materials produced were characterized by XRD, SEM, EDS-mapping, and N<SUB>2</SUB> adsorption-desorption measurements. S-IRMOF-3(p) exhibited satisfactory CO<SUB>2</SUB> adsorption capacities (54 mg/g at 298 K/1 bar; 732 mg/g at 298 K/20 bar) and CO<SUB>2</SUB>/N<SUB>2</SUB> selectivity (18 at 298 K/1 bar). Both S-IRMOF-3(Mem) and S-IRMOF-3(p) were assessed as a catalyst for a liquid phase Knoevenagel condensation reaction between benzaldehyde and ethyl cyanoacetate. S-IRMOF-3(Mem) and S-IRMOF-3(p) showed comparable conversions (87-89%) with 100% selectivity after a 4 h reaction at 333 K. The heterogeneous nature of the catalyst was confirmed by a hot filtering experiment, and S-IRMOF-3(Mem) could be recovered easily after the reaction and be recycled several times with little change in product yield.

Relationship Between K_trans and K₁ with Simultaneous Versus Separate MR/PET in Rabbits with VX2 Tumors

Lee, K. H.,Kang, S. K.,Goo, J. M.,Lee, J. S.,Cheon, G. J.,Seo, S.,Hwang, E. J. INTERNATIONAL INSTITUTE OF ANTICANCER RESEARCH 2017 Anticancer research Vol.37 No.3

<P>Background/Aim: To compare the relationship between Ktrans from DCE-MRI and K1 from dynamic (NNH3)-N-13- PET, with simultaneous and separate MR/PET in the VX-2 rabbit carcinoma model. Materials and Methods: MR/PET was performed simultaneously and separately, 14 and 15 days after VX-2 tumor implantation at the paravertebral muscle. The Ktrans and K-1 values were estimated using an in-house software program. The relationships between Ktrans and K-1 were analyzed using Pearson's correlation coefficients and linear/non-linear regression function. Results: Assuming a linear relationship, Ktrans and K-1 exhibited a moderate positive correlations with both simultaneous ( r=0.54-0.57) and separate ( r=0.53-0.69) imaging. However, while the Ktrans and K-1 from separate imaging were linearly correlated, those from simultaneous imaging exhibited a non-linear relationship. The amount of change in K-1 associated with a unit increase in Ktrans varied depending on Ktrans values. Conclusion: The relationship between K-trans and K-1 may be mis-interpreted with separate MR and PET acquisition.</P>

K₂WO₄ flux 에 의한 K₂Oㆍ6TiO₂ whisker 의 합성

이진식 ( J. S. Lee ),이상문 ( S. M. Lee ),이철태 ( C. T. Lee ),권긍택 ( K. T. Kohn ),김영명 ( Y. M. Kim ) 한국공업화학회 1993 한국공업화학회 연구논문 초록집 Vol.1993 No.0

K₂Oㆍ6TiO₂ whisker는 구조적인 특성 때문에 물리ㆍ화학적으로 매우 안정하며 보강재, 마찰재, 단열재 등의 많은 용도를 갖게된다. 특히 최근에는 석면이 발암물질로 인한 자동차 브레이크 마찰재료의 사용이 금지됨에 따라 K₂Oㆍ6TiO₂ whisker는 이의 대체 섬유로서 주목을 받고 있다. 이러한 K₂Oㆍ6TiO₂ whisker의 합성방법으로는 TiO₂와 K₂CO₃의 화학양론적 조성의 혼합들을 설정온도에서 소성(calcination method)시키는 방법을 비롯하여 응용법(melting method), 수열법(hydrothermal method), 융제법(flux) 및 KDC법(kneading-drying-calcination method) 등의 방법이 있다. 그러나 수열법의 경우 양질의 whisker를 얻을 수 있으나 고압합성 이므로 위험하고 가격이 비싼 결점이 있으며 공업상 제조에 필요한 조건이 복잡하고 연속조작이 어려워 비현실적인 방법이다. 또한 서냉소성법의 경우 공정이 단순하며 공업화가 쉬우나 비교적 장섬유가 얻어지게 된다. 따라서 본 연구에서는 융제법을 이용하여 K₂Oㆍ6TiO₂ whisker를 합성하였으며. 과거에 용제로 사용된 KC1-KF계. K₂O-Na₂O-B₂O₃계 등의 높은 volatility와 viscosity 그리고 낮은 solubility에 대한 문제점을 개선하기 위해 K₂WO₄를 flux로 선정하여 K₂Oㆍ6TiO₂ whisker를 합성하였다.

1H Nuclear Magnetic Resonance study of Ferroelectric (NH4)3H(SO4)2

S. H. Choi,K. S. Han,S. K. Kwon,S. K. Nam,H. H. Choi,Moohee Lee,Ae Ran Lim 한국자기공명학회 2007 Journal of the Korean Magnetic Resonance Society Vol.11 No.2

1H nuclear magnetic resonance (NMR) experiments have been performed at 30 - 300 K and 7 T to investigate dynamics of hydrogen bond network in the single crystal (NH4)3H(SO4)2. The two proton sites, ammonium proton and hydrogen-bond proton, are identified from the 1H NMR MAS spectrum at 340 K. As temperature decreases, the 1H NMR spectrum shifts to the higher frequency side with a larger linewidth. The spectrum at 65 K shows a distinctive change in line shape toward the ferroelectric transition at 63 K. The measured values of T1 for ammonium and hydrogen-bond protons are similar in the whole range of temperature. T1 of 1H NMR shows a gradual decrease down to 120 K and starts to steeply increase below 100 K. Then T1 shows abrupt decrease below 70 K with a sharp minimum at 63 K, where the ferroelectric transition occurs. This temperature dependence of spectrum and T1 clearly prove that the large change in the dynamics of hydrogen bond network is associated with the ferroelectric phase transition at 63 K.

Predicting temporal shifts in the spring occurrence of overwintered Scotinophara lurida (Hemiptera: Pentatomidae) and rice phenology in Korea with climate change

Lee, H.,Kang, W. S.,Ahn, M. I.,Cho, K.,Lee, J. H. Springer Science + Business Media 2016 International journal of biometeorology Vol.60 No.1

<P>Climate change could shift the phenology of insects and plants and alter their linkage in space and time. We examined the synchrony of rice and its insect pest, Scotinophara lurida (Burmeister), under the representative concentration pathways (RCP) 8.5 climate change scenario by comparing the mean spring immigration time of overwintered S. lurida with the mean rice transplanting times in Korea. The immigration time of S. lurida was estimated using an overwintered adult flight model. The rice transplanting time of three cultivars (early, medium, and medium-late maturing) was estimated by forecasting the optimal cultivation period using leaf appearance and final leaf number models. A temperature increase significantly advanced the 99 % immigration time of S. lurida from Julian day 192.1 in the 2000s to 178.4 in the 2050s and 163.1 in the 2090s. In contrast, rice transplanting time was significantly delayed in the early-maturing cultivar from day 141.2 in the 2000s to 166.7 in the 2050s and 190.6 in the 2090s, in the medium-maturing cultivar from day 130.6 in the 2000s to 156.6 in the 2050s and 184.7 in the 2090s, and in the medium-late maturing cultivar from day 128.5 in 2000s to 152.9 in the 2050s and 182.3 in the 2090s. These simulation results predict a significant future phenological asynchrony between S. lurida and rice in Korea.</P>

The prolyl isomerase Pin1 interacts with a ribosomal protein S6 kinase to enhance insulin-induced AP-1 activity and cellular transformation

Lee, N. Y.,Choi, H.-K.,Shim, J.-H.,Kang, K.-W.,Dong, Z.,Choi, H. S. Oxford University Press 2009 Carcinogenesis Vol.30 No.4

<P>Phosphorylation of proteins on serine or threonine residues that immediately precede proline (pSer/Thr-Pro) is specifically catalyzed by the peptidyl-prolyl cis-trans isomerase Pin1 and is a central signaling mechanism in cell proliferation and transformation. Although Pin1 is frequently overexpressed in hepatocellular carcinoma (HCC), the molecular mechanism of Pin1 in HCC has not been completely elucidated. Here, we show that Pin1 interacts with p70S6K in vitro and ex vivo. Overexpression of Pin1 resulted in enhanced p70S6K phosphorylation induced by insulin in SK-HEP-1 cells. In contrast, Pin1(-/-) mouse embryonic fibroblasts (MEFs) exhibited significantly decreased insulin-induced p70S6K phosphorylation compared with Pin1(+/+) MEFs. Furthermore, Pin1 enhanced the insulin-induced extracellular signal-regulated protein kinase (ERK)1/2 phosphorylation through its interaction with p70S6K, whereas the inhibition of p70S6K activity by rapamycin suppressed insulin-induced ERK1/2 phosphorylation in SK-HEP-1 cells. Hence, Pin1 affected activator protein-1 activity through p70S6K-ERK1/2 signaling in SK-HEP-1 cells. Most importantly, Pin1-overexpressing JB6 Cl41 cells enhanced neoplastic cell transformation promoted by insulin much more than green fluorescent protein-overexpressing JB6 Cl41 control cells. These results imply that Pin1 amplifies insulin signaling in hepatocarcinoma cells through its interaction with p70S6K, suggesting that Pin1 plays an important role in insulin-induced tumorigenesis and is a potential therapeutic target in hepatocarcinoma.</P>

Novel dentin phosphoprotein frameshift mutations in dentinogenesis imperfecta type II

Lee, K‐,E,Kang, H‐,Y,Lee, S‐,K,Yoo, S‐,H,Lee, J‐,C,Hwang, Y‐,H,Nam, KH,Kim, J‐,S,Park, J‐,C,Kim, J‐,W Blackwell Publishing Ltd 2011 Clinical genetics Vol.79 No.4

<P>Lee K‐E, Kang H‐Y, Lee S‐K, Yoo S‐H, Lee J‐C, Hwang Y‐H, Nam KH, Kim J‐S, Park J‐C, Kim J‐W. Novel dentin phosphoprotein frameshift mutations in dentinogenesis imperfecta type II.</P><P>The dentin sialophosphoprotein (<I>DSPP</I>) gene encodes the most abundant non‐collagenous protein in tooth dentin and DSPP protein is cleaved into several segments including the highly phosphorylated dentin phosphoprotein (DPP). Mutations in the <I>DSPP</I> gene have been solely related to non‐syndromic form of hereditary dentin defects. We recruited three Korean families with dentinogenesis imperfecta (DGI) type II and sequenced the exons and exon–intron boundaries of the <I>DSPP</I> gene based on the candidate gene approach. Direct sequencing of PCR products and allele‐specific cloning of the highly repetitive exon 5 revealed novel single base pair (bp) deletional mutations (c.2688delT and c.3560delG) introducing hydrophobic amino acids in the hydrophilic repeat domain of the DPP coding region. All affected members of the three families showed exceptionally rapid pulp chambers obliteration, even before tooth eruption. Individuals with the c.3560delG mutation showed only mild, yellowish tooth discoloration, in contrast to the affected individuals from two families with c.2688delT mutation. We believe that these results will help us to understand the molecular pathogenesis of DGI type II as well as the normal process of dentin biomineralization.</P>

Reactivities of organic isothiocyanates and thiocyanates toward dialkyl bis(phosphine) complexes of palladium(II) and platinum(II)

Lee, S.G.,Choi, K.Y.,Kim, Y.J.,Park, S.,Lee, S.W. Pergamon Press 2015 Polyhedron Vol.85 No.-

Room-temperature reactions of trans-[PdEt<SUB>2</SUB>L<SUB>2</SUB>] (L=PMe<SUB>3</SUB>, PEt<SUB>3</SUB>, PMe<SUB>2</SUB>Ph) with organic isothiocyanates [R-NCS; R=benzyl; CH(CH<SUB>3</SUB>)Ph, R-(-) and S-(+); indanyl, S-(+)] afforded the S,S-coordinated Pd(II) complexes [Pd(S<SUB>2</SUB>C?N-R)L<SUB>2</SUB>] containing a dithiocarbonimidato (S<SUB>2</SUB>C?N-R) group. Similar reactions involving allyl isothiocyanates produced the cationic η<SUP>3</SUP>-allyl Pd complex [Pd(η<SUP>3</SUP>-allyl)(PMe<SUB>3</SUB>)<SUB>2</SUB>]<SUP>+</SUP>(NCS)<SUP>-</SUP>. When [Pd(S<SUB>2</SUB>C?N-R)(PMe<SUB>3</SUB>)<SUB>2</SUB>] was treated with 1equiv of a chelating phosphine [L-L=depe (1,2-bis(diethylphosphino)ethane) and dmpe (1,2-bis(dimethylphosphino)ethane)], the corresponding complexes [Pd(S<SUB>2</SUB>C?N-R)(L-L)] were produced. Reactions of trans-[PdEt<SUB>2</SUB>L<SUB>2</SUB>] (L=PMe<SUB>3</SUB>, PMe<SUB>2</SUB>Ph) with organic thiocyanates (R-SCN; R=benzyl, Et) resulted in the formation of [Pd(CN)<SUB>2</SUB>L<SUB>2</SUB>] and an organic disulfide by S-C bond cleavage of R-SCN. However, similar reactions of the dimethyl analogs, trans-[PdMe<SUB>2</SUB>L<SUB>2</SUB>] (L=PMe<SUB>3</SUB>, PEt<SUB>3</SUB>), with benzyl thiocyanate afforded different products, [Pd(NCS)<SUB>2</SUB>L<SUB>2</SUB>] or [PdMe(NCS)L<SUB>2</SUB>]. Treating [Pt(styrene)(PMe<SUB>3</SUB>)<SUB>2</SUB>] with benzyl isothiocyanate gave the S-coordinated dithiocarbonimidato Pt(II) complex, [Pt(S<SUB>2</SUB>C?N-R)(Me<SUB>3</SUB>P)<SUB>2</SUB>] (R=benzyl). In contrast, cis-[PtEt<SUB>2</SUB>(PMe<SUB>3</SUB>)<SUB>2</SUB>] reacted with the isothiocyanate to afford the trialkyl Pt(IV) complex [PtEt<SUB>2</SUB>(SCN)(CH<SUB>2</SUB>Ph)(PMe<SUB>3</SUB>)<SUB>2</SUB>].