• 제목/요약/키워드: molecular processes

검색결과 1,228건 처리시간 0.026초

Post-Translational Regulation of the RSF1 Chromatin Remodeler under DNA Damage

  • Min, Sunwoo;Choi, Yong Won;Yun, Hansol;Jo, Sujin;Ji, Jae-Hoon;Cho, Hyeseong
    • Molecules and Cells
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    • 제41권2호
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    • pp.127-133
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    • 2018
  • Chromatin remodeling factors are involved in many cellular processes such as transcription, replication, and DNA damage response by regulating chromatin structure. As one of chromatin remodeling factors, remodeling and spacing factor 1 (RSF1) is recruited at double strand break (DSB) sites and regulates ataxia telangiectasia mutated (ATM) -dependent checkpoint pathway upon DNA damage for the efficient repair. RSF1 is overexpressed in a variety of cancers, but regulation of RSF1 levels remains largely unknown. Here, we showed that protein levels of RSF1 chromatin remodeler are temporally upregulated in response to different DNA damage agents without changing the RSF1 mRNA level. In the absence of SNF2h, a binding partner of RSF1, the RSF1 protein level was significantly diminished. Intriguingly, the level of RSF1-3SA mutant lacking ATM-mediated phosphorylation sites significantly increased, and upregulation of RSF1 levels under DNA damage was not observed in cells overexpressing ATM kinase. Furthermore, failure in the regulation of RSF1 level caused a significant reduction in DNA repair, whereas reconstitution of RSF1, but not of RSF1-3SA mutants, restored DSB repair. Our findings reveal that temporal regulation of RSF1 levels at its post-translational modification by SNF2h and ATM is essential for efficient DNA repair.

Identification of the Antidepressant Vilazodone as an Inhibitor of Inositol Polyphosphate Multikinase by Structure-Based Drug Repositioning

  • Lee, Boah;Park, Seung Ju;Lee, Seulgi;Park, Seung Eun;Lee, Eunhye;Song, Ji-Joon;Byun, Youngjoo;Kim, Seyun
    • Molecules and Cells
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    • 제43권3호
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    • pp.222-227
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    • 2020
  • Inositol polyphosphate multikinase (IPMK) is required for the biosynthesis of inositol phosphates (IPs) through the phosphorylation of multiple IP metabolites such as IP3 and IP4. The biological significance of IPMK's catalytic actions to regulate cellular signaling events such as growth and metabolism has been studied extensively. However, pharmacological reagents that inhibit IPMK have not yet been identified. We employed a structure-based virtual screening of publicly available U.S. Food and Drug Administration-approved drugs and chemicals that identified the antidepressant, vilazodone, as an IPMK inhibitor. Docking simulations and pharmacophore analyses showed that vilazodone has a higher affinity for the ATP-binding catalytic region of IPMK than ATP and we validated that vilazodone inhibits IPMK's IP kinase activities in vitro. The incubation of vilazodone with NIH3T3-L1 fibroblasts reduced cellular levels of IP5 and other highly phosphorylated IPs without influencing IP4 levels. We further found decreased Akt phosphorylation in vilazodone-treated HCT116 cancer cells. These data clearly indicate selective cellular actions of vilazodone against IPMK-dependent catalytic steps in IP metabolism and Akt activation. Collectively, our data demonstrate vilazodone as a method to inhibit cellular IPMK, providing a valuable pharmacological agent to study and target the biological and pathological processes governed by IPMK.

Rapamycin-Induced Abundance Changes in the Proteome of Budding Yeast

  • Shin, Chun-Shik;Chang, Yeon-Ji;Lee, Hun-Goo;Huh, Won-Ki
    • Genomics & Informatics
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    • 제7권4호
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    • pp.203-207
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    • 2009
  • The target of rapamycin (TOR) signaling pathway conserved from yeast to human plays critical roles in regulation of eukaryotic cell growth. It has been shown that TOR pathway is involved in several cellular processes, including ribosome biogenesis, nutrient response, autophagy and aging. However, due to the functional diversity of TOR pathway, we do not know yet some key effectors of the pathway. To find unknown effectors of TOR signaling pathway, we took advantage of a green fluorescent protein (GFP)-tagged collection of budding yeast Saccharomyces cerevisiae. We analyzed protein abundance changes by measuring the GFP fluorescence intensity of 4156 GFP-tagged yeast strains under inhibition of TOR pathway. Our proteomic analysis argues that 83 proteins are decreased whereas 32 proteins are increased by treatment of rapamycin, a specific inhibitor of TOR complex 1 (TORC1). We found that, among the 115 proteins that show significant changes in protein abundance under rapamycin treatment, 37 proteins also show expression changes in the mRNA levels by more than 2-fold under the same condition. We suggest that the 115 proteins indentified in this study may be directly or indirectly involved in TOR signaling and can serve as candidates for further investigation of the effectors of TOR pathway.

척수손상 후 세포이식에 의한 운동기능의 회복증진 (Improvement of Functional Recovery by Cell Transplantation after Spinal Cord Injury)

  • 이배환;이경희;성제경;황세진;김계성
    • 감성과학
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    • 제7권2호
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    • pp.179-186
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    • 2004
  • 중추신경계는 일단 손상이 되면 손상된 세포의 재생, 손상된 수초의 회복, 신경계의 정상적인 연결 등의 제한성 때문에 그 회복이 매우 힘들다. 이러한 중추신경계의 중요한 손상으로는 다발성 경화증, 뇌졸중, 척수손상, 외상, 축삭의 탈수초화 등이 있다. 이전 연구들은 많은 발생빈도를 보이고 있는 척수손상에서 실질적인 척수의 기능적인 회복을 위해 손상된 척수신경의 재생과 축삭의 재수초화가 중요한 요인이라고 전하고 있다. 최근에는 이러한 척수손상에 대한 치료적 접근으로서 세포이식 기술이 하나의 해결책을 열어주고 있다. 따라서 본 논문에서는 척수손상의 특성을 살펴보고, 척수손상에 의한 기능장애에 대해 세포이식이 기능의 회복을 증진시킬 수 있다는 증거를 논의하고자 한다.

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Physiological and Genetic Mechanisms for Nitrogen-Use Efficiency in Maize

  • Mi, Guohua;Chen, Fanjun;Zhang, Fusuo
    • Journal of Crop Science and Biotechnology
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    • 제10권2호
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    • pp.57-63
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    • 2007
  • Due to the strong influence of nitrogen(N) on plant productivity, a vast amount of N fertilizers is used to maximize crop yield. Over-use of N fertilizers leads to severe pollution of the environment, especially the aquatic ecosystem, as well as reducing farmer's income. Growing of N-efficient cultivars is an important prerequisite for integrated nutrient management strategies in both low- and high-input agriculture. Taking maize as a sample crop, this paper reviews the response of plants to low N stress, the physiological processes which may control N-use efficiency in low-N input conditions, and the genetic and molecular biological aspects of N-use efficiency. Since the harvest index(HI) of modern cultivars is quite high, further improvement of these cultivars to adapt to low N soils should aim to increase their capacity to accumulate N at low N levels. To achieve this goal, establishment and maintenance of a large root system during the growth period may be essential. To reduce the cost of N and carbon for root growth, a strong response of lateral root growth to nitrate-rich patches may be desired. Furthermore, a large proportion of N accumulated in roots at early growth stages should be remobilized for grain growth in the late filling stage to increase N-utilization efficiency. Some QTLs and genes related to maize yield as well as root traits have been identified. However, their significance in improving maize NUE at low N inputs in the field need to be elucidated.

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A whole genomic scan to detect selection signatures between Berkshire and Korean native pig breeds

  • Edea, Zewdu;Kim, Kwan-Suk
    • Journal of Animal Science and Technology
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    • 제56권7호
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    • pp.23.1-23.7
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    • 2014
  • Background: Scanning of the genome for selection signatures between breeds may play important role in understanding the underlie causes for observable phenotypic variations. The discovery of high density single nucleotide polymorphisms (SNPs) provide a useful starting point to perform genome-wide scan in pig populations in order to identify loci/candidate genes underlie phenotypic variation in pig breeds and facilitate genetic improvement programs. However, prior to this study genomic region under selection in commercially selected Berkshire and Korean native pig breeds has never been detected using high density SNP markers. To this end, we have genotyped 45 animals using Porcine SNP60 chip to detect selection signatures in the genome of the two breeds by using the $F_{ST}$ approach. Results: In the comparison of Berkshire and KNP breeds using the FDIST approach, a total of 1108 outlier loci (3.48%) were significantly different from zero at 99% confidence level with 870 of the outlier SNPs displaying high level of genetic differentiation ($F_{ST}{\geq}0.490$). The identified candidate genes were involved in a wide array of biological processes and molecular functions. Results revealed that 19 candidate genes were enriched in phosphate metabolism (GO: 0006796; ADCK1, ACYP1, CAMK2D, CDK13, CDK13, ERN1, GALK2, INPP1; MAK, MAP2K5, MAP3K1, MAPK14, P14KB, PIK3C3, PRKC1, PTPRK, RNASEL, THBS1, BRAF, VRK1). We have identified a set of candidate genes under selection and have known to be involved in growth, size and pork quality (CART, AGL, CF7L2, MAP2K5, DLK1, GLI3, CA3 and MC3R), ear morphology and size (HMGA2 and SOX5) stress response (ATF2, MSRB3, TMTC3 and SCAF8) and immune response (HCST and RYR1). Conclusions: Some of the genes may be used to facilitate genetic improvement programs. Our results also provide insights for better understanding of the process and influence of breed development on the pattern of genetic variations.

분광분석을 활용한 고에너지 레이저 환경에서의 알루미늄-산소 화학반응 연구 (The spectroscopic study of chemical reaction of laser-ablated aluminum-oxygen by high power laser)

  • 김창환
    • 한국항공우주학회지
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    • 제44권9호
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    • pp.789-795
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    • 2016
  • 이차 추진제로 많이 쓰이는 알루미늄을 고출력 레이저를 조사하여 공기 중의 산소와 반응시켜 발생되는 알루미늄과 산소의 화학 반응을 레이저 분광분석법을 이용하여 연구를 수행 하였다. 7ns의 펄스 주기와 1064nm의 주파수를 가진 Q-switched Nd:YAG 레이저로 40 - 2500mJ($6.88{\times}10^{10}-6.53{\times}10^{11}W/cm^2$)의 에너지가 공급되었으며, 플라즈마 빛은 echelle 회절 분광기와 ICCD 카메라로 감지하였다. 분광분석을 통하여 알루미늄과 산소의 원자/분자 신호 분석과 현상이 일어나는 플라즈마 환경의 특성 연구를 위해 들뜸 온도(2200K~6600K) 및 전자밀도($3.15{\times}10^{15}{\sim}2.38{\times}10^{16}cm^{-3}$) 계산, 그리고 알루미늄 표면의 크레이터(Crater) 분석을 수행하였다. 본 연구는 고 레이저 복사 조도 환경하에서 발생되는 화학 반응과 플라즈마의 특성을 파악하는 방법을 제시하고 있다.

Netrin-1 Specifically Enhances Cell Spreading on Fibronectin in Human Glioblastoma Cells

  • Lee, Hyun-Kyoung;Seo, In-Ae;Shin, Yoon-Kyung;Lee, Sang-Hwa;Seo, Su-Young;Suh, Duk-Joon;Park, Hwan-Tae
    • The Korean Journal of Physiology and Pharmacology
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    • 제12권5호
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    • pp.225-230
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    • 2008
  • Netrins are secreted molecules and involved in axon guidance, cell migration and tumor development. Recent studies revealed that netrins perform novel functions in such processes as epithelial development and angiogenesis without operating through the classical netrin receptors, DCC (Deleted in Colorectal Cancer) and Unc5h. In the present study, we investigated the roles of netrin-1 and its receptors in cell spreading of human glioblastoma cells, and found that netrin-1 haptotactically enhanced fibronectin-induced cell spreading and focal adhesion formation in U373 glioblastoma cells. Netrin-1 binding to the U373 cell membrane was blocked by an antibody against ${\alpha}v$ integrin subunit, but not by an anti-DCC or anti-Unc5h antibody. In addition, enhancement of the fibronectin response by netrin-1 was abrogated by a function blocking antibody against integrin ${\alpha}v{\beta}3$. Since the ${\alpha}v$ subunit of the integrin family plays an important role in the pathophysiological aspects of cell migration, including tumor angiogenesis and metastasis, our data provide important insight into the molecular mechanism of netrin function.

Comparative Analyses of Tomato yellow leaf curl virus C4 Protein-Interacting Host Proteins in Healthy and Infected Tomato Tissues

  • Kim, Namgyu;Kim, Jinnyun;Bang, Bongjun;Kim, Inyoung;Lee, Hyun-Hee;Park, Jungwook;Seo, Young-Su
    • The Plant Pathology Journal
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    • 제32권5호
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    • pp.377-387
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    • 2016
  • Tomato yellow leaf curl virus (TYLCV), a member of the genus Begomovirus, is one of the most important viruses of cultivated tomatoes worldwide, mainly causing yellowing and curling of leaves with stunting in plants. TYLCV causes severe problems in sub-tropical and tropical countries, as well as in Korea. However, the mechanism of TYLCV infection remains unclear, although the function of each viral component has been identified. TYLCV C4 codes for a small protein involved in various cellular functions, including symptom determination, gene silencing, viral movement, and induction of the plant defense response. In this study, through yeast-two hybrid screenings, we identified TYLCV C4-interacting host proteins from both healthy and symptom-exhibiting tomato tissues, to determine the role of TYLCV C4 proteins in the infection processes. Comparative analyses of 28 proteins from healthy tissues and 36 from infected tissues showing interactions with TYLCV C4 indicated that TYLCV C4 mainly interacts with host proteins involved in translation, ubiquitination, and plant defense, and most interacting proteins differed between the two tissues but belong to similar molecular functional categories. Four proteins-two ribosomal proteins, S-adenosyl-L-homocysteine hydrolase, and 14-3-3 family protein-were detected in both tissues. Furthermore, the identified proteins in symptom-exhibiting tissues showed greater involvement in plant defenses. Some are key regulators, such as receptor-like kinases and pathogenesis-related proteins, of plant defenses. Thus, TYLCV C4 may contribute to the suppression of host defense during TYLCV infection and be involved in ubiquitination for viral infection.

Characterization of Hibiscus Latent Fort Pierce Virus-Derived siRNAs in Infected Hibiscus rosa-sinensis in China

  • Lan, Han-hong;Lu, Luan-mei
    • The Plant Pathology Journal
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    • 제36권6호
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    • pp.618-627
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    • 2020
  • Although limited progress have been made about pathogen system of Hibiscus rosa-sinensis and Hibiscus latent Fort Pierce virus (HLFPV), interaction between plant host and pathogen remain largely unknown, which led to deficiency of effective measures to control disease of hibiscus plants caused by HLFPV. In this study, infection of HLFPV in Hibiscus rosa-sinensis was firstly confirmed for the first time by traditional electron microscopy, modern reverse transcription polymerase chain reaction and RNA-seq methods in China (HLFPV-Ch). Sequence properties analyzing suggested that the full-length sequences (6,465 nt) of HLFPV-Ch had a high sequence identity and a similar genomic structure with other tobamoviruses. It includes a 5'-terminal untranslated region (UTR), followed by four open reading frames encoding for a 128.5-kDa replicase, a 186.5-kDa polymerase, a 31-kDa movement protein, 17.6-kDa coat protein, and the last a 3'-terminal UTR. Furthermore, HLFPV-Ch-derived virus-derived siRNAs (vsiRNAs) ant its putative target genes, reported also for the first time, were identified and characterized from disease Hibiscus rosa-sinensis through sRNA-seq and Patmatch server to investigate the interaction in this pathogen systems. HLFPV-Ch-derived vsiRNAs demonstrated several general and specific characteristics. Gene Ontology classification revealed predicted target genes by vsiRNAs are involved in abroad range of cellular component, molecular function and biological processes. Taken together, for first time, our results certified the HLFPV infection in China and provide an insight into interaction between HLFPV and Hibiscus rosa-sinensis.