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SF3B4 Depletion Retards the Growth of A549 Non-Small Cell Lung Cancer Cells via UBE4B-Mediated Regulation of p53/p21 and p27 Expression

  • Kim, Hyungmin;Lee, Jeehan;Jung, Soon-Young;Yun, Hye Hyeon;Ko, Jeong-Heon;Lee, Jeong-Hwa
    • Molecules and Cells
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    • 제45권10호
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    • pp.718-728
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    • 2022
  • Splicing factor B subunit 4 (SF3B4), a component of the U2-pre-mRNA spliceosomal complex, contributes to tumorigenesis in several types of tumors. However, the oncogenic potential of SF3B4 in lung cancer has not yet been determined. The in vivo expression profiles of SF3B4 in non-small cell lung cancer (NSCLC) from publicly available data revealed a significant increase in SF3B4 expression in tumor tissues compared to that in normal tissues. The impact of SF3B4 deletion on the growth of NSCLC cells was determined using a siRNA strategy in A549 lung adenocarcinoma cells. SF3B4 silencing resulted in marked retardation of the A549 cell proliferation, accompanied by the accumulation of cells at the G0/G1 phase and increased expression of p27, p21, and p53. Double knockdown of SF3B4 and p53 resulted in the restoration of p21 expression and partial recovery of cell proliferation, indicating that the p53/p21 axis is involved, at least in part, in the SF3B4-mediated regulation of A549 cell proliferation. We also provided ubiquitination factor E4B (UBE4B) is essential for p53 accumulation after SF3B4 depletion based on followings. First, co-immunoprecipitation showed that SF3B4 interacts with UBE4B. Furthermore, UBE4B levels were decreased by SF3B4 depletion. UBE4B depletion, in turn, reproduced the outcome of SF3B4 depletion, including reduction of polyubiquitinated p53 levels, subsequent induction of p53/p21 and p27, and proliferation retardation. Collectively, our findings indicate the important role of SF3B4 in the regulation of A549 cell proliferation through the UBE4B/p53/p21 axis and p27, implicating the therapeutic strategies for NSCLC targeting SF3B4 and UBE4B.

Development of a Sequence Characteristic Amplified Region Marker linked to the L4 Locus Conferring Broad Spectrum Resistance to Tobamoviruses in Pepper Plants

  • Kim, Hyun Jung;Han, Jung-Heon;Yoo, Jae Hyoung;Cho, Hwa Jin;Kim, Byung-Dong
    • Molecules and Cells
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    • 제25권2호
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    • pp.205-210
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    • 2008
  • To develop molecular markers linked to the $L^4$ locus conferring resistance to tobamovirus pathotypes in pepper plants, we performed AFLP with 512 primer combinations for susceptible (S pool) and resistant (R pool) DNA bulks against pathotype 1.2 of pepper mild mottle virus. Each bulk was made by pooling the DNA of five homozygous individuals from a T10 population, which was a near-isogenic $BC_4F_2$ generation for the $L^4$ locus. A total of 19 primer pairs produced scorable bands in the R pool. Further screening with these primer pairs was done on DNA bulks from T102, a $BC_{10}F_2$ derived from T10 by back crossing. Three AFLP markers were finally selected and designated L4-a, L4-b and L4-c. L4-a and L4-c each underwent one recombination event, whereas no recombination for L4-b was seen in 20 individuals of each DNA bulk. Linkage analysis of these markers in 112 $F_2$ T102 individuals showed that they were each within 2.5 cM of the $L^4$ locus. L4-b was successfully converted into a simple 340-bp SCAR marker, designated L4SC340, which mapped 1.8 cM from the $L^4$ locus in T102 and 0.9 cM in another $BC_{10}F_2$ population, T101. We believe that this newly characterized marker will improve selection of tobamovirus resistance in pepper plants by reducing breeding cost and time.

A 6.4-Gb/s/channel Asymmetric 4-PAM Transceiver for Memory Interface

  • 이광훈;장영찬
    • 한국정보통신학회:학술대회논문집
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    • 한국해양정보통신학회 2011년도 춘계학술대회
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    • pp.129-131
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    • 2011
  • Hight speed memory application을 위하여 6.4-Gb/s/channel 4-PAM transceiver가 제안된다. Voltage margin과 time margin용 증가시키기 위하여 asymmetric 4-PAM scheme과 이를 위한 회로를 제안한다. 제안된 asymmetric 4-PAM scheme은 기존 회로에 비하여 송신단에서 33%의 기준전압 노이즈 영향을 줄인다. Channel의 ISI를 줄이기 위해서 transmitter의 1-tap pre-emphasis가 사용된다. 제안된 asymmetric 4-PAM transceiver는 1.2V supply 0.13um 1-poly 6-metal CMOS 공정에서 구현되었다. PLL을 포함한 1-channel transceiver의 면적과 전력소모는 각각 $0.294um^2$와 6mW이다.

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활성제 첨가에 따른 ZnGa2O4 형광체의 발광특성 (Luminescence Characteristics of ZnGa2O4 Phosphors with the Doped Activator)

  • 홍범주;최형욱
    • 한국전기전자재료학회논문지
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    • 제19권5호
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    • pp.432-436
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    • 2006
  • The $ZnGa_2O_4$ and Mn, Cr-doped $ZnGa_2O_4$ Phosphors were synthesized through conventional solid state reactions. The XRD patterns show that the $ZnGa_2O_4$ has a (3 1 1) main peak and a spinel phase. The emission wavelength of $ZnGa_2O_4$ showed main peak of 420 nm and maximum intensity at the sintering temperature of $1100^{\circ}C$. In the crystalline $ZnGa_2O_4$, the Mn shows green emission (510 nm, $^4T_1-^6A_1$) with a quenching concentration of 0.6 mol%, and the Cr shows red emission (705 nm, $^4T_2-^4A_2$) with a quenching concentration of 2 mol%. These results indicate that $ZnGa_2O_4$ Phosphors hold promise for potential applications in field emission display devices with high brightness operating in full color regions.

4-Chlorophenol 분해박테리아 Arthrobacter chlorophenolicus A6로부터의 monooxygenase의 복제 및 대량발현과 정제 그리고 기질분해활성도 분석 (Overexpression and Purification of Monooxygenases Cloned from Arthrobacter chlorophenolicus A6 for Enzymatic Decomposition of 4-Chlorophenol)

  • 류송정;이소라;김한승
    • 한국지하수토양환경학회지:지하수토양환경
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    • 제19권3호
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    • pp.47-55
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    • 2014
  • Arthrobacter chlorophenolicus A6 possesses several monooxygenases (CphC-I, CphC-II, and CphB) that can catalyze the transformation of 4-chlorophenol (4-CP) to hydroxylated intermediates in the initial steps of substrate metabolism. The corresponding genes of the monooxygenases were cloned, and the competent cells were transformed with these recombinant plasmids. Although CphC-II and CphB were expressed as insoluble forms, CphC-I was successfully expressed as a soluble form and isolated by purification. The specific activity of the purified CphC-I was analyzed by using 4-CP, 4-chlorocatechol (4-CC), and catechol (CAT) as substrates. The specific activities for 4-CP, 4-CC, and CAT were determined to be 0.312 U/mg, 0.462 U/mg, 0.246 U/mg, respectively. The results of this study indicated that CphC-I is able to catalyze the degradation of 4-CC and CAT in addition to 4-CP, which is a primary substrate. This research is expected to provide the fundamental information for the development of an eco-friendly biochemical degradation of aromatic hydrocarbons.

Investigation of the Reaction of 6-Amino-3-methyl-4-oxo-3, 4-dihydro-2-pyrimidinylhydrazine

  • Moustafa, M.A.;Gineinah, M.M.;Bayomi, S.M.;Ismaiel, A.M.
    • Archives of Pharmacal Research
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    • 제13권4호
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    • pp.347-350
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    • 1990
  • The hydrazine derivative 2 has been utilized for the synthesis of three different fused 1, 2, 4-triazolo [4, 3-a] pyrimidine derivatives 4, 5, &6 and a tetrazolo [1, 5-a] pyrimidine derivative 7. Reaction of 2 with the chalcone analogue 2-thenylidene-2'-acetothienone, gave the pyrazoline derivative 8.

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Synthesis and Structure of Benzotriazolyl Fluorenes

  • KohPark, Kwang-Hee;Jung, Hye-Mi;Lee, Tae-Woo;Kang, Sung-Kwon
    • Bulletin of the Korean Chemical Society
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    • 제31권4호
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    • pp.984-988
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    • 2010
  • 1-(Fluoren-2-yl)-benzo[d][1,2,3]triazoles 5a-b were synthesized starting from 2-nitrofluorene. 2-Nitrofluorenes 1a-b were reduced by catalytic hydrogenation, reacted with 2,4-dinitrofluorobenzene followed by catalytic hydrogenation to afford 2-(N-2,4-diaminophenyl)aminofluorenes 4a-b. Diazotization of 4a-b with $NaNO_2/H_2SO_4$ followed by treatment with $H_3PO_2$ gave 5a-b. Sulfonation of 5a-b yielded 7-benzotriazol-1-yl-fluorene-2-sulfonic acids 6a-b. The structures of 5b and 6b were firmly identified by X-ray crystal analysis in addition to $^1H$ NMR, $^{13}C$ NMR, and elemental analysis.

쏘가리(Siniperca scherzeri) 젖산탈수소효소 A4 동위효소의 정제 및 특성 (Purification and Characterization of Lactate Dehydrogenase A4 Isozyme in Mandrin Fish (Siniperca scherzeri))

  • 조성규;구보라;안효정;박은미;박선영;김재범;염정주
    • 생명과학회지
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    • 제19권2호
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    • pp.256-263
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    • 2009
  • 쏘가리 젖산탈수소효소(EC 1.1.1.27, lactate dehydrogenase, LDH) $A_4$ 동위효소를 affinity chromatography 및 ultrafiltration으로 정제하였다. 정제된 LDH $A_4$ 동위효소의 분자량은 140.4 kDa이었고 등전점(pI)은 7.0이었다. 효소반응의 최적 pH는 7.5로 나타났다. 피루브산을 기질로 하였을 때 LDH $A_4$ 동위효소의 ${K_m}^{PYR}$값은 $4.86{\times}10^{-5}$ M, $V_{max}$값은 13.31mM/min로 나타났다. LDH $A_4$ 동위효소의 역학실험은 쏘가리가 온수성어류라는 점을 보여주었고 정제된 LDH $A_4$ 동위 효소에 대한 항체는 변온 척추동물의 대사생리학적 특성을 연구하거나 여러 가지 병증의 진단에 유용하게 사용될 수 있을 것이다.

돼지 MC4R 유전자 892G>A 다형성이 비육돈의 도체형질에 미치는 영향 (Effects of a Porcine MC4R Polymorphism(892G>A) on Carcass Traits in Commercial Pigs)

  • 한상현;이성수;고문석;성필남;박범영;조인철
    • Journal of Animal Science and Technology
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    • 제49권5호
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    • pp.569-576
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    • 2007
  • 임의적으로 선정된 비육돈 집단에서 melano- cortin-4 receptor(MC4R) 유전자의 유전적 변이와 도체형질의 연관성을 조사하였다. 돼지 MC4R 유전자형은 Asp298Asn(nt. 892G>A) 돌연변이를 PCR-RFLP 방법으로 결정하였다. 비육돈 집단에서 유전자형 A/A, A/G, G/G가 모두 출현하였고, 빈도는 각각 28.8, 48.4, 22.8%를 나타내었다. 전체 비육돈에서 유전자형 A/-은 G/G에 비해 근내지방도가 유의적으로 높게 나타났다(P<0.05). 동형접합자 A/A와 G/G가 이형접합자 A/G인 도체에 비해 육색도는 더 낮고 수분삼출도는 높은 것으로 확인되었다(P<0.01). 반면, -/G인 거세돈의 도체중이 A/A에 비해 도체중이 유의적으로 무겁게(약 2.5kg) 나타났다(P<0.05). 각 유전자형의 도체형질에 대한 효과는 미경산돈에서는 전체 비육돈 집단에 대한 효과와 유사하나, 거세돈 집단과는 다소 차이가 있었고, 이는 도체형질에 대한 현재까지 알려지지 않은 성-관련 효과로 추정된다. 본 연구에서 비육돈 생산에 있어 MC4R A/- 유전자형이 육질을 향상시킬 수 있을 것으로 기대된다. 하지만, MC4R 유전자형들이 성과 관련되어 차별적으로 도체형질에 영향을 주고 있기 때문에, 비육돈 생산을 위한 marker-assisted selection을 위해서는 성과 유전자형 모두가 고려되어져야 할 것이다.