• Title/Summary/Keyword: Ras protein

Search Result 172, Processing Time 0.028 seconds

Design of Novel Ras Farnesyltransferase Inhibitors Based on Virtual Screening and Docking Studies

  • Jung, Kang-Rae;Park, Hyung-Yeon;Kim, Chan-Kyung;Lee, Bon-Su
    • Proceedings of the PSK Conference
    • /
    • 2003.10b
    • /
    • pp.175.2-175.2
    • /
    • 2003
  • Inhibition of the protein-modifying enzyme farnesyltransferase is considered as a major emerging strategy in cancer therapy because of the involvement of farnesylated proteins in oncogensis. We studied the structure-activity relationship of a novel class of CAAX-peptidomimetic farnesyltransferase inhibitors based on the benzophenone scaffold. FlexX docking of inhibitors confirmed reasonable fit of the molecule into the peptide binding site of farnesyltransferase. We also performed a virtual screening with LeadQuest chemical library databases to idenfity novel inhibitors of farnesyltransferase. (omitted)

  • PDF

The mRNA Expression of Radio-Sensitive Genes Exposed to Various Dosage of Ionizing Radiation in U-937 Cell (U-937 세포에서 이온화 방사선의 조사선량에 따른 감수성 유전자들의 발현 변화)

  • 김종수;임희영;오연경;김인규;강경선;윤병수
    • Toxicological Research
    • /
    • v.20 no.1
    • /
    • pp.21-29
    • /
    • 2004
  • We used cDNA microarray to assess gene expression profiles in hematopoetic cell line, U-937, exposed to low doses of ionizing irradiation. The 1,000 DNA elements on this array were PCR-amplified cDNAs selected from named human cancer related genes. According to the strength of irradiation, the levels of some gene expression were increased or decreased as dose-dependent manner. The gene expressions of Tubulin alpha, protein kinase, interferon-alpha, -beta, -omega receptor and ras homolog gene family H were significantly increased. Especially, Tubulin gene was shown 2.5 fold up-regulated manner under stress of 500 rad irradiation than 200 rad. On the other hand, fibroblast growth factor 12 and four and a half LIM domains, etc. were significantly down-regu-lated. Also, tumor protein 53(TP53) related genes that p53 inducible protein, tumor protein 53-binding protein looks of little significance as radiation sensitive manner. The radio-sensitivity of tubulin gene etc. that we proposed could be useful to rapid and correct survey for the bio-damage by exposure to low dose irradiation.

Small Molecules Targeting for ESX-Sur2 Proteins' Interaction

  • Kwon, Young-Joo
    • Proceedings of the Korean Society of Applied Pharmacology
    • /
    • 2008.04a
    • /
    • pp.77-86
    • /
    • 2008
  • It's been known that overexpression of the oncoprotein Her2 (eu/ErbB2), transmembrane receptor protein, occurs in human breast cancer. Her2-positive breast cancer patients who have Her2 overexpression show less therapeutic efficacy with enhanced metathesis and increased resistance to chemotherapy. So far, a humanized monoclonal antibody against Her2 protein called Herceptin is the only drug approved by Food and Drug Administration for treatment of Her2-overexpressing breast tumors. However, antibody therapy of Herceptin may not be ideal method for therapeutic intervention of Her2 protein expression. The therapeutic intervention of Her2 protein expression may be more efficiently achieved by inhibiting the expression of Her2 gene rather than by down-regulating the Her2 protein already overexpressed. Here, we found that the interaction of two proteins of ESX (an epithelial-restricted transcription factor) and DRIP130/CRSP130/Sur2 (a Ras-linked subunit of human mediator complexes) mediates the expression of Her2 gene. The association of ESX with Sur2 is mediated by a small hydrophobic face of 8-amino acid helix in ESX, suggesting that the ESX-Sur2 interaction can be a new novel target for Her2-positive cancer. The process to develop potent ESX-Sur2 interaction inhibitors targeting for Her2-positive cancer therapeutics will be discussed.

  • PDF

Identification of Differentially Expressed Genes by TCDD in Human Bronchial Cells: Toxicogenomic Markers for Dioxin Exposure

  • Park, Chung-Mu;Jin, Kyong-Suk;Lee, Yong-Woo
    • Biomedical Science Letters
    • /
    • v.18 no.1
    • /
    • pp.1-9
    • /
    • 2012
  • Differentially expressed genes by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were identified in order to evaluate them as dioxin-sensitive markers and crucial signaling molecules to understand dioxin-induced toxic mechanisms in human bronchial cells. Gene expression profiling was analyzed by cDNA microarray and ten genes were selected for further study. They were cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1), S100 calcium binding protein A8 (calgranulin A), S100 calcium binding protein A9 (calgranulin B), aldehyde dehydrogenase 1 family, member A3 (ALDH6) and peroxiredoxin 5 (PRDX5) in up-regulated group. Among them, CYP1B1 was used as a hallmark for dioxin and sharply increased by TCDD exposure. Down-regulated genes were IK cytokine, interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), nuclease sensitive element binding protein 1 (NSEP1), protein tyrosine phosphatase type VI A, member 1 (PTP4A1), ras oncogene family 32 (RAB32). Although up-regulated 4 genes in microarray were coincided with northern hybridization, down-regulated 5 genes showed U-shaped expression pattern which is sharply decreased at lower doses and gradually increased at higher doses. These results introduce some of TCDD-responsive genes can be sensitive markers against TCDD exposure and used as signaling cues to understand toxicity initiated by TCDD inhalation in pulmonary tissues.

Prognostic Factors in Children with Henoch-$Sch{\ddot{o}}nlein$ Purpura Nephritis (소아 Henoch-$Sch{\ddot{o}}nlein$ 신염의 예후 인자)

  • Choi Hyun Jin;Cho Hee Yeon;Kim Eo Jin;Lee Byong Sop;Kang Hee Gyung;Ha Il Soo;Cheong Hae Il;Choi Yong
    • Childhood Kidney Diseases
    • /
    • v.9 no.2
    • /
    • pp.183-192
    • /
    • 2005
  • Purpose : The long term disease course and prognostic factors were evaluated in childhood Henoch-$Sch{\ddot{o}}nlein$ puruura nephritis(HSPN). Methods : A total of 75 children(44 boys and 31 girls) with HSPN were included in this study. The onset age was $8.0{\pm}3.1$ years(2.3-l5.3 years), and the follow-up period was $4.3{\pm}3.6$ years(1.0-17.1 years). Kidney biopsy was done in 24 children(32$\%$). Initial clinical and laboratory findings were evaluated. In addition, polymorphisms of the renin angiotensin system(RAS) genes(insertion/deletion in intron 16 of ACE gene, M235T in AGT gene, and A1166C in AGTR gene) were analysed. The initial and last clinical states were classified into 4 groups as follows A, normal; B, minor urinary abnormalities; C, active renal disease (nephrotic-range proteinuria and/or hypertension with serum creatinine $\leq$1.5 mg/dL); D, renal insufficiency. Results : At the onset, the clinical states of the patients were B in 26(35$\%$), C in 46(61$\%$), and D, in 3(4$\%$). The distribution of the RAS gene polymorphism of HSPN were not different from that of 100 healthy control subjects. At the last follow-up, the clinical states of the patients were A in 23(31$\%$), B in 38(50$\%$), C in 9(12$\%$), and D in 5(7$\%$). A multiple logistic regression identified age at the onset and initial urine protein excretion as significant prognostic factors. Analysis of genotypes of the 3 RAS genes as prognostic values revealed no statistical significance. Conclusion : Older age at onset and severe proteinuria were identified as poor prognostic factors of childhood HSPN. Implication of the RAS gene polymorphism In HSPN could not be validated in this small-scale retrospective study. (J Korean Soc Pediatr Nephrol 2005;9:183-192)

  • PDF

Fecal Solid Feed from the Recirculating Aquaculture System of the Renewable Sea Cucumber Apostichopus japonicus (해삼사료원료로서 육상순환여과양식장 고형오물의 이화학적 특징과 해삼(Apostichopus japonicus)의 소화흡수율)

  • Jeong, U-Cheol;Jin, Feng;Choi, Jong-Kuk;Md, Anisuzzaman;Choi, Byeong-Dae;Kang, Seok-Joong
    • Korean Journal of Fisheries and Aquatic Sciences
    • /
    • v.49 no.3
    • /
    • pp.330-336
    • /
    • 2016
  • Pollution caused by fecal solids released from recirculating aquaculture systems (RAS) is a growing global concern requiring immediate attention. Thus, this study investigated the physicochemical characteristics of fecal solid feed from RASs used for eel and rainbow trout farming. The concentrations of proteins, lipids, crude ash, and moisture in eel fecal solids were 10.9%, 1.2%, 85.8%, and 72.2%, respectively, while those in rainbow trout fecal solid feed were 20.5%, 3.2%, 70.9%, and 87.0%, respectively. The control group was fed a mixture of sea cucumber and dried sea mud. The protein digestibilities of eel and rainbow trout fecal solids were 25.43% and 23.96%, respectively, while the respective lipid digestibilities were 35.62% and 36.80%, respectively.

Emerging Genomics Technologies in Nutritional Sciences: Applications to obesity and hypertension research

  • Mouss, Naima-Moustaid;Sumithra Urs;Kim, Suyeon;Heo, Young-Ran
    • Proceedings of the Korean Nutrition Society Conference
    • /
    • 2002.05a
    • /
    • pp.29-41
    • /
    • 2002
  • While the sequencing of several genomes was underway, several advanced techniques in genetics, molecular biology and protein chemistry emerged. Within the nutritional sciences, while the focus on nutrition education, epidemiology and public health aspects remains essential; it is crucial to incorporate the new advances in gene and protein discovery in nutritional studies. Nutrition is a discipline that has always integrated social, biochemical and physiological sciences from the studies at the molecule level to studies at the population level. For this reason, nutritionists are in a prime position to readily incorporate the current genomics approaches in nutrition research, All the available analytical techniques can and should be used in modern nutritional sciences. These include genetics, genomics, proteomics and metabolomics which also require integration and use of bioinformatics and computational methods for data analysis and management. These applications will be briefly reviewed with a primary focus on what the genomics and genetics approaches offer to nutritionists. We will use one of our research focus areas to illustrate uses of some of these applications in obesity-hypertension research. Our central hypothesis is that adipose tissue is an endocrine organ that plays a major role in obesity and related hypertension. We are primarily studying the renin angiotensin system (RAS). We provide evidence from our own studies and others for the paracrine as well as endocrine role of adipocyte-derived angiotensin II in adipocyte gene expression, adiposity and blood pressure regulation. Both cell culture studies as well as knockout and transgenic mice models are used to test our hypothesis. Genomics and proteomics technologies are currently developed to complement our physiological and molecular studies on the RAS and for a fine analysis of this system and its function in health and disease.

  • PDF

Emerging Genomics Technologies in Nutritional Sciences : Applications to Obesity and Hypertension Research

  • Moustaid-Moussa;Sumithra Urs;Kim, Suyeon;Heo, Young-Ran
    • Proceedings of the Korean Nutrition Society Conference
    • /
    • 2002.06a
    • /
    • pp.598-603
    • /
    • 2002
  • While the sequencing of several genomes was underway, several advanced techniques in genetics, molecular biology and protein chemistry emerged. Within the notritional sciences, while the focus on nutrition education, epidemiology and public health aspects remains essential; it is crucial to incorporate the new advances in gene and protein discovery in nutritional studies. Nutrition is a discipline that has always integrated social, biochemical and physiological sciences from the studies at the molecule level to studies at the population level. for this reason, nutritionists are in a prime position to readily incorporate the current genomics approaches in nutrition research. All the available analytical techniques can and should be used in modem nutritional sciences. These include genetics, genomics, proteomics and metabolomics which also require integration and use of bioinformatics and computational methods for data analysis and management. These applications will be briefly reviewed with a primary focus on what the genomics and genetics approaches offer to nutritionists. We will use one of our research focus areas to illustrate uses of some of these applications in obesity-hypertension research. Our central hypothesis is that adipose tissue is an endocrine organ that plays a major role in obesity and related hypertension. We are primarily studying the renin angiotensin system (RAS). We provide evidence from our own studies and others for the paracrine as well as endocrine role of adipocyte-derived angiotensin II in adipocyte gene expression, adiposity and blood pressure regulation. Both cell culture studies as well as knockout and transgenic mice models are used to test our hypothesis. Genomics and proteomics technologies are currently developed to complement our physiological and molecular studies on the RAS and for a fine analysis of this system and its function in health and disease.

  • PDF

Effect of Different Feeding Frequency on the Growth Performance, Hematological Parameters and Body Nutrient Composition of Juvenile Chum Salmon Oncorhynchus keta Reared in a Recirculating Aquaculture System (순환여과양식시스템에서 사료 공급 횟수가 연어(Oncorhynchus keta) 치어의 성장, 체조성 및 혈액성분에 미치는 영향)

  • Kyu-Seok Cho;Seok-Woo Jang;Yu-Jin Lee;Seunghyung Lee
    • Korean Journal of Fisheries and Aquatic Sciences
    • /
    • v.56 no.5
    • /
    • pp.734-740
    • /
    • 2023
  • The effect of feeding frequency on growth performance, body nutrient composition, and hematological parameters of juvenile chum salmon Oncorhynchus keta was investigated. The juveniles (10.9±0.3 g) were fed commercial feed for 30 days with feeding frequencies of 1, 2, 3, 4, or 5 meal (s)/day (n=2 tanks per treatment) in a recirculating aquaculture system (RAS). Fish were fed to satiation at each of the feeding frequencies. At the end of the feeding trial, final body weight, weight gain, and specific growth rate of fish fed 2 meals/day were significantly higher than those of fish fed 1 meal/day(P<0.05); however, no difference was detected among the other feeding frequencies. Daily feed intake significantly increased with increasing feeding frequency, whereas feed and protein utilization efficiencies continuously decreased with increase in the feeding frequency. Among the treatments, fish fed 1 meal/day showed the lowest value in whole-body lipid content and total protein concentration in plasma. Taken together, the optimal feeding frequency for growth performance and feed utilization efficiency in chum salmon juveniles reared in the RAS was determined to be 2 meals/day.