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Suppressor of Variegation 3-9 Homolog 2, a Novel Binding Protein of Translationally Controlled Tumor Protein, Regulates Cancer Cell Proliferation

  • Kim, A-Reum;Sung, Jee Young;Rho, Seung Bae;Kim, Yong-Nyun;Yoon, Kyungsil
    • Biomolecules & Therapeutics
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    • v.27 no.2
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    • pp.231-239
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    • 2019
  • Suppressor of Variegation 3-9 Homolog 2 (SUV39H2) methylates the lysine 9 residue of histone H3 and induces heterochromatin formation, resulting in transcriptional repression or silencing of target genes. SUV39H1 and SUV39H2 have a role in embryonic development, and SUV39H1 was shown to suppress cell cycle progression associated with Rb. However, the function of human SUV39H2 has not been extensively studied. We observed that forced expression of SUV39H2 decreased cell proliferation by inducing $G_1$ cell cycle arrest. In addition, SUV39H2 was degraded through the ubiquitin-proteasomal pathway. Using yeast two-hybrid screening to address the degradation mechanism and function of SUV39H2, we identified translationally controlled tumor protein (TCTP) as an SUV39H2-interacting molecule. Mapping of the interacting regions indicated that the N-terminal 60 amino acids (aa) of full-length SUV39H2 and the C-terminus of TCTP (120-172 aa) were critical for binding. The interaction of SUV39H2 and TCTP was further confirmed by co-immunoprecipitation and immunofluorescence staining for colocalization. Moreover, depletion of TCTP by RNAi led to up-regulation of SUV39H2 protein, while TCTP overexpression reduced SUV39H2 protein level. The half-life of SUV39H2 protein was significantly extended upon TCTP depletion. These results clearly indicate that TCTP negatively regulates the expression of SUV39H2 post-translationally. Furthermore, SUV39H2 induced apoptotic cell death in TCTP-knockdown cells. Taken together, we identified SUV39H2, as a novel target protein of TCTP and demonstrated that SUV39H2 regulates cell proliferation of lung cancer cells.

SUV39H1 is a New Client Protein of Hsp90 Degradated by Chaetocin as a Novel C-Terminal Inhibitor of Hsp90

  • Lian, Bin;Lin, Qian;Tang, Wei;Qi, Xin;Li, Jing
    • Biomolecules & Therapeutics
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    • v.29 no.1
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    • pp.73-82
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    • 2021
  • Hsp90 is often overexpressed with activated form in cancer cells, and many key cellular proteins are dependent upon the Hsp90 machinery (these proteins are called "client protein"). Nowadays, more client proteins and more inhibitors of Hsp90 are being discovered. Chaetocin has been identified as an inhibitor of histone methyl transferase SUV39H1. Herein, we find that Chaetocin is an inhibitor of Hsp90 which binds to the C-terminal of Hsp90α. Chaetocin inhibited a variety of Hsp90 client proteins including AMl1-ETO and BCL-ABL, the mutant fusion-protein in the K562 and HL-60 cells. SUV39H1 mediates epigenetic events in the pathophysiology of hematopoietic disorders. We found that inhibition of Hsp90 by Chaetocin and 17-AAG had ability to induce degradation of SUV39H1 through proteasome pathway. In addition, SUV39H1 interacted with Hsp90 through co-chaperone HOP. These results suggest that SUV39H1 belongs to a client protein of Hsp90. Moreover, Chaetocin was able to induce cell differentiation in the two cells in the concentration range of Hsp90 inhibition. Altogether, our results demonstrate that SUV39H1 is a new client protein of Hsp90 degradated by Chaetocin as a novel C-terminal inhibitor of Hsp90. The study establishes a new relationship of Chaetocin and SUV39H1, and paves an avenue for exploring a new strategy to target SUV39H1 by inhibition of Hsp90 in leukemia.

Dephosphorylation of p53 Ser 392 Enhances Trimethylation of Histone H3 Lys 9 via SUV39h1 Stabilization in CK2 Downregulation-Mediated Senescence

  • Park, Jeong-Woo;Bae, Young-Seuk
    • Molecules and Cells
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    • v.42 no.11
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    • pp.773-782
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    • 2019
  • Cellular senescence is an irreversible form of cell cycle arrest. Senescent cells have a unique gene expression profile that is frequently accompanied by senescence-associated heterochromatic foci (SAHFs). Protein kinase CK2 (CK2) downregulation can induce trimethylation of histone H3 Lys 9 (H3K9me3) and SAHFs formation by activating SUV39h1. Here, we present evidence that the PI3K-AKT-mTOR-reactive oxygen species-p53 pathway is necessary for CK2 downregulation-mediated H3K9me3 and SAHFs formation. CK2 downregulation promotes SUV39h1 stability by inhibiting its proteasomal degradation in a p53-dependent manner. Moreover, the dephosphorylation status of Ser 392 on p53, a possible CK2 target site, enhances the nuclear import and subsequent stabilization of SUV39h1 by inhibiting the interactions between p53, MDM2, and SUV39h1. Furthermore, $p21^{Cip1/WAF1}$ is required for CK2 downregulation-mediated H3K9me3, and dephosphorylation of Ser 392 on p53 is important for efficient transcription of $p21^{Cip1/WAF}$. Taken together, these results suggest that CK2 downregulation induces dephosphorylation of Ser 392 on p53, which subsequently increases the stability of SUV39h1 and the expression of $p21^{Cip1/WAF1}$, leading to H3K9me3 and SAHFs formation.

EBP1 regulates Suv39H1 stability via the ubiquitin-proteasome system in neural development

  • Kim, Byeong-Seong;Ko, Hyo Rim;Hwang, Inwoo;Cho, Sung-Woo;Ahn, Jee-Yin
    • BMB Reports
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    • v.54 no.8
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    • pp.413-418
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    • 2021
  • ErbB3-binding protein 1 (EBP1) is a multifunctional protein associated with neural development. Loss of Ebp1 leads to upregulation of the gene silencing unit suppressor of variegation 3-9 homolog 1 (Suv39H1)/DNA (cytosine 5)-methyltransferase (DNMT1). EBP1 directly binds to the promoter region of DNMT1, repressing DNA methylation, and hence, promoting neural development. In the current study, we showed that EBP1 suppresses histone methyltransferase activity of Suv39H1 by promoting ubiquitin-proteasome system (UPS)-dependent degradation of Suv39H1. In addition, we showed that EBP1 directly interacts with Suv39H1, and this interaction is required for recruiting the E3 ligase MDM2 for Suv39H1 degradation. Thus, our findings suggest that EBP1 regulates UPS-dependent degradation of Suv39H1 to govern proper heterochromatin assembly during neural development.

Ethanol Production an Immobilized Themotolerant Mutant of Brettanomyces custersii H1-39 from Wood Hydrolyzate Media (목질계 당화액배지로부터 고온내성 변이주 Brettanomyces custersii H1-39의 고정화에 의한 에탄올생산)

  • 박승원;홍영기;김승욱;홍석인
    • Microbiology and Biotechnology Letters
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    • v.28 no.3
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    • pp.172-179
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    • 2000
  • Bretlanomyces C!tstersii Hl-39 mutant was immobilized with various caniers. Immobilized mutant Hl-39 produced more ethanol and showed higher productivity and cell concentration than those of free 81-39 in 3.4% hydrolyzate of wood-chips at different temperatures ($37^{\circ}C$, $40^{\circ}C$ and $43^{\circ}C$). At $37^{\circ}C$, ethanol concentration produced by mutant H1-39 immobilized in Ca-alginate and ARG(l % Ca-alginate, 1.67% bentonite, 0.33% glutaraldehyde) bead were higher than those produced by the other earners (ACG ; 1 % CaHalginate. ] .67% celite R-634 , 0.33% glutaraldehyde, ABP ; 1 % Ca-alginate. 1.67% bentonite, 0.33% pectin. ACP: 1 % Ca-alginate, ] .67% celiLe R-634, 0.33% pecLin). The highest value of productivity(l.23 ) was obtained by using ABG beads. At $40^{\circ}C$, ethanol conccntration and productivity obtained by ABC beads ,>,"ere 15.2 glL and 0.84 gl L.h, respectively, which showed the highest value compared to other carriers. Particularly, productivity of ilmnobilized ceIl was increased up to 90% as compared to that offree cell. On the other hand, ABP(l % Ca-alginate+L67% bentonile+O.33% pectin) beads gave the best resulLs at $43^{\circ}C$ for production of ethanol and productivity, which were 13.8 g!l and 0.77 g/l h, respectively.ively.

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Development of Strain Fermenting the Glucose/Cellbiose Mixed Sugar for Simultaneous Saccharification of Fermentation of Cellulosic Materials (섬유소 물질의 동시당화발효에 적합한 Glucose/Cellbiose 혼합당 발효균주의 개발)

  • 박승원;홍영기;김승욱;홍석인
    • Microbiology and Biotechnology Letters
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    • v.27 no.2
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    • pp.145-152
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    • 1999
  • Brettanomyces custersii CBS 5512 which has reported as a thermotolerant glucose-cellobiose co-fermentable yeast strain was mutated with UV and NTG to improve ethanol yield at higher than 4$0^{\circ}C$ B. custersii H1-23, H1-39, H1-55 and H1062 were finally selected for hyper-fermentable strains at higher than 4$0^{\circ}C$ from thermotolerant 7510 colonies through 5th selection. Among the selected strains, H1-39 mutant had better fermentability at 4$0^{\circ}C$ and 43$^{\circ}C$ from different concentrations of glucose. H1-39 and H1-23 mutants yielded more than 70% of the theoretical ethanol yield in 4 and 8% mixed sugars at above 4$0^{\circ}C$, which was 5-11% higher than those by original strain. Especially, H1-39 mutant had better fermentability in 4% mixed sugar. It showed 78.5% of the theoretical yield at 4$0^{\circ}C$ and 72.2% of the theoretical yield at 43$^{\circ}C$. On the other hand, theoretical yield of ethanol by H1-39 mutant in 8% mixed sugar at 4$0^{\circ}C$ and 43$^{\circ}C$ were 75.2% and 70.2%, respectively. Theses values increased up to 7-11% as compared to those by orginal strain. By the simultaneous saccharification and fermentation, ethanol production by H1-39 mutant increased up to more than 23% as compared to that by original strain.

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Study on Waxy Corn X. Analysis on Botanical Characteristics, Physicochemical Properties Related to Table Qualities of the Developed Waxy Corn Hybrids (찰옥수수 연구 X. 육성된 찰옥수수 교잡종의 식물학적 특성 및 식미관련 이화학적 형질)

  • Lee, Moon-Sub;Bok, Tae-Gyu;Choi, Yun-Pyo;Hong, Bom-Young;Jo, Yang-Hee;Lee, Hee-Bong
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.56 no.1
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    • pp.8-13
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    • 2011
  • This study was carried out to compare botanical characteristics, physicochemical properties related to table quality and feed values and develop a new variety among 12 developed waxy com hybrids. These materials were produced in 2008 and cultivated in 2009 at Com Breeding and Genetics Farm of Coll. of Agri. & Life Sci., Chungnam Nat'l Univ. Botanical characteristics of used waxy com hybrids showed large difference among hybrids; stem height, ear height and ear length. In physical properties, range of kernel sugar content among used hybrids appeared 16.1 to 13.0brix(%). CNU08H-15, CNU08H-35 and CNU08H-h39 among these were highly appeared as 15 above and pericarp thickness of Yeonongchal was very thick as $46.0{\mu}m$, while CNU08H-39 among hybrids showed the thinnest as $23.0{\mu}m$ compared to other hybrids. Protein content as a indicator of table quality was the highest in Ilmichal among hybrids, while that of CNU08H-39 was the lowest, while amylopectin content was the highest as 94.5%, From experimental results, Daehakchal Gold 1, CNU08H-h121 and CNU08H-39 including check Yeonyoungchal were highly evaluated as new hybrid in thinner pericarp, high amylopectin and chewiness.

MAPPING PROPERTIES OF THE MARCINKIEWICZ INTEGRALS ON HOMOGENEOUS GROUPS

  • Choi, Young-Woo;Rim, Kyung-Soo
    • Journal of the Korean Mathematical Society
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    • v.39 no.1
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    • pp.61-75
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    • 2002
  • Under the cancellation property and the Lipschitz condition on kernels, we prove that the Marcinkiewicz integrals defined on a homogeneous group H are bounded from $H^1$(H) to $L^1$(H), from $L_{c}$ $^{\infty}$(H) to BMO (H), and from $L^{p}$ (H) to $L^{p}$ (H) for 1 < p < $\infty$ assuming the $L^{q}$ -boundedness for some q > 1.for some q > 1.

Synthesis and Properties of Uranium Compounds (I). Salts of Bis(undecatungstophosphato)uranate(Ⅳ) Anion, $[U(PW_{11}O_{39})_2]^{10-}$ (우라늄 화합물의 합성과 성질에 관한 연구 (제1보). 비스(운데카텅스토포스파토)우라늄(IV) 산 이온, $[U(PW_{11}O_{39})_2]^{10-}$의 염)

  • Chul Wee Lee;Hyunsoo So
    • Journal of the Korean Chemical Society
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    • v.26 no.3
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    • pp.160-164
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    • 1982
  • A guanidinium salt of $[U(PW_{11}O_{39})_2]^{10-}$, the solubility of which is adequate for crystal growing, has been synthesized. Using this salt or potassium salt, we have measured the stability of $[U(PW_{11}O_{39})_2]^{10-}$as a function of pH of the solution and found that the anion is stable for the pH range 3~7. We have developed a colorimetric method for determining the concentration of $U^{4+}$. In this method$PW_{11}O_{39}^{7-}$ is added to$U^{4+}$ in such a quantity that the mole ratio $PW_{11}O_{39}^{7-}/ U^{4+}$exceeds 2 and the intensity of the 22.7kK band (${\varepsilon}$1030 M-1cm-1) is measured. In order to develop a continuous method to recover uranium, we have determined the amount of recoverd$PW_{11}O_{39}^{7-}$ after decomposing $[U(PW_{11}O_{39})_2]^{10}$- by adding either a base or an oxidizing agent. The percentage of $PW_{11}O_{39}^{7-}$recovered was approximately 70% when a base was used and approximately 80% when$K_2S_2O_8$ was used. A colorimetric method for determining $PW_{11}O_{39}^{7-}$ has also been developed.

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