Genomine Inc.

Pohang, South Korea

Genomine Inc.

Pohang, South Korea
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Kim I.S.,Kyungpook National University | Shin S.-Y.,Kyungpook National University | Kim Y.-S.,Kyungpook National University | Kim H.-Y.,Kyungpook National University | And 4 more authors.
Journal of Microbiology and Biotechnology | Year: 2010

Cyclophilins contain the conserved activity of cis-trans peptidyl-prolyl isomerase, which is implicated in protein folding, and function as molecular chaperones. When the yeast cyclophilin A gene (cpr1) was subcloned into the prokaryotic expression vector pKM260, it was found that the expression of Cpr1 drastically increased the cell viability of E. coli BL21 when under abiotic stress conditions, as in the presence of cadmium, copper, hydrogen peroxide, heat, and SDS. Therefore, this study illustrates the importance of Cpr1 as a molecular chaperone that can improve the cellular stress responses when E. coli cells are exposed to adverse conditions, while also demonstrating its potential to increase the stability of E. coli strains utilized for the production of recombinant proteins. © The Korean Society for Microbiology and Biotechnology.

Kim I.-S.,Kyungpook National University | Kim H.-Y.,Kyungpook National University | Shin S.-Y.,Kyungpook National University | Kim Y.-S.,Kyungpook National University | And 3 more authors.
Molecules and Cells | Year: 2010

Cyclophilins are conserved cis-trans peptidyl-prolyl isomerase that are implicated in protein folding and function as molecular chaperones. We found the expression of cyclophilin A, Cpr1, changes in response to exposure to yeast Saccharomyces cerevisiae to abiotic stress conditions. The effect of Cpr1 overexpression in stress responses was therefore examined. The CPR1 gene was cloned to the yeast expression vector pVTU260 under regulation of an endogenous alcohol dehydrogenase (ADH) promoter. The overexpression of Cpr1 drastically increased cell viability of yeast in the presence of stress inducers, such as cadmium, cobalt, copper, hydrogen peroxide, tert-butyl hydroperoxide (t-BOOH), and sodium dodecyl sulfate (SDS). The Cpr1 expression also enhanced the cell rescue program resulting in a variety of antioxidanr enzymes including thioredoxin system (particularly, thioredoxin peroxidase), metabolic enzymes (glucose-6-phosphate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase), and molecular chaperones (Hsp104, Hsp90, Hsp60 and Hsp42). Thus, our study illustrates the importance of Cpr1 as a molecular chaperone that improves cellular stress responses through collaborative relationships with other proteins when yeast cells are exposed to adverse conditions, and it also premises the improvement of yeast strains. © 2010 The Korean Society for Molecular and Cellular Biology and Springer Netherlands.

Choi H.,Korea Basic Science Institute | Choi H.,Pohang University of Science and Technology | Jeong S.,Korea Basic Science Institute | Jeong S.,Pohang University of Science and Technology | And 10 more authors.
Physiologia Plantarum | Year: 2014

Phytochromes are red (R)/far-red (FR) photoreceptors that are central to the regulation of plant growth and development. Although it is well known that photoactivated phytochromes are translocated into the nucleus where they interact with a variety of nuclear proteins and ultimately regulate genome-wide transcription, the mechanisms by which these photoreceptors function are not completely understood. In an effort to enhance our understanding of phytochrome-mediated light signaling networks, we attempted to identify novel proteins interacting with phytochrome B (phyB). Using affinity purification in Arabidopsis phyB overexpressor, coupled with mass spectrometry analysis, 16 proteins that interact with phyB in vivo were identified. Interactions between phyB and six putative phyB-interacting proteins were confirmed by bimolecular fluorescence complementation (BiFC) analysis. Involvement of these proteins in phyB-mediated signaling pathways was also revealed by physiological analysis of the mutants defective in each phyB-interacting protein. We further characterized the athb23 mutant impaired in the homeobox protein 23 (ATHB23) gene. The athb23 mutant displayed altered hypocotyl growth under R light, as well as defects in phyB-dependent seed germination and phyB-mediated cotyledon expansion. Taken together, these results suggest that the ATHB23 transcription factor is a novel component of the phyB-mediated R light signaling pathway. © 2013 Scandinavian Plant Physiology Society.

Kang S.,Yonsei University | Shim H.S.,Yonsei University | Lee J.S.,Bruker | Kim D.S.,Genomine Inc. | And 5 more authors.
Journal of Proteome Research | Year: 2010

The specific molecular profiles of ovarian cancer interface zones (IZ), the region between tumors and normal tissues, were evaluated using a new method involving matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS). We analyzed three ovarian serous carcinomas using MALDI-IMS. Principal component analysis (PCA) was used to evaluate the quality of tissue spatial features based on MALDI-IMS, and for analysis of large data sets of MALDI-IMS. Twodimensional gel electrophoresis and fluorescence microscopy were used to verify interface-specific proteins. Unique profiles were identified for the tumors, the normal zone, and the IZ. Through MALDI analysis, two interfacespecific proteins, plastin 2 and peroxiredoxin 1 (PRDX 1), were identified as differentially regulated between zones. Fluorescence microscopy revealed high expression levels of plastin 2 and PRDX 1 along the IZ of ovarian tumors. This comparative proteomics study using tissue MALDIIMS suggested that the IZ is different from the adjacent tumor and normal zones, and that plastin 2 and PRDX 1 may be interface markers specific to ovarian tumors. © 2010 American Chemical Society.

Kim D.S.,Research South, Inc. | Kim D.S.,Genomine Inc. | Choi Y.P.,Yonsei University | Kang S.,Yonsei University | And 13 more authors.
Journal of Proteome Research | Year: 2010

The timely diagnosis and therapeutic monitoring of human renal cell carcinoma (RCC) is limited by the lack of specific biomarkers. To identify candidate RCC biomarkers, we used 2-DE gel electrophoresis with mass spectrometry and 2-DE spot intensity-based ROC analysis to analyze 18 sets of paired normal and RCC tumor tissue including conventional, papillary, and chromophobe subtypes. Validation was performed with RCC patient plasma samples and confirmed by clustergram, shRNA, and immunohistochemistry assays. Cardinal candidates were evaluated by ELISA. The leading candidate biomarker that was upregulated in RCC samples according to the clustergram and validation analysis was nicotinamide N-methyltransferase (NNMT) (13/15, P < 0.0001). Other upregulated candidate biomarkers that were identified by this method include ferritin, hNSE, NM23, secretagogin, and l-plastin. The upregulation of NNMT in RCC was confirmed by immunoblotting and immunohistochemistry. Analysis of fractionated membrane-associated proteins identified CAP-G, mitofillin, tubulin aα, RBBP7, and HSP27. Of these, RBBP7 and HSP27 were highly expressed in the chromophobe subtype of RCC (3/3) but were absent from conventional RCC (0/3). The triple combination of the NNMT, FTL, and hNSE biomarkers had the highest predictive capacity of 0.993, while NNMT was the single, most powerful candidate diagnostic biomarker for all types of RCC. © 2010 American Chemical Society.

Kang S.,Yonsei University | Kim M.J.,Yonsei University | An H.,Pundang CHA Medical Hospital | Kim B.G.,Yonsei University | And 9 more authors.
Journal of Proteome Research | Year: 2010

Surgical tumor margins are intended to encompass residual tumor cells but may not always accurately delineate the boundary between tumor and normal tissue. Efforts to define tumor margins based on molecular analysis have achieved limited success. Furthermore, no clinical trials have addressed the scope of the tumor microenvironment. Here, we considered the tumor cell population and surrounding microenvironment in delineating tumor margins, classifying breast cancer into tumor and normal zones, and introducing the concept of an interface zone, the region between the invading tumor front and normal tissue, which develops during tumor invasion and metastasis through remodeling of the tumor microenvironment. Pathological signatures of invasion markers in tumor tissues are most dynamic within the invading tumor front. We compared protein profiles of tumor, normal, and interface zones using MALDI-MS. Proteins upregulated in the interface zone were identified by peptide mass fingerprinting and confirmed by database searching with chemically assisted MALDI-PSD spectra. Upregulation was confirmed for RhoGDIα, CAPG, WDR1, and CK8 by Western and immunohistochemical analyses. Our results demonstrate that the molecular profile of the interface zone is unique and suggest that upregulation of proteins here may be related to progression and metastasis of breast carcinomas. © 2010 American Chemical Society.

Hwang I.-T.,Korea Research Institute of Chemical Technology | Choi J.-S.,Korea Research Institute of Chemical Technology | Song H.-Y.,Korea Research Institute of Chemical Technology | Cho S.-J.,Korea Research Institute of Chemical Technology | And 3 more authors.
Pesticide Biochemistry and Physiology | Year: 2010

The validation of potential herbicide target, 7-keto-8-aminopelargonic acid synthase (KAPAS) in the early step of biotin biosynthesis pathway, was performed in vitro and in vivo with lead chemical triphenyltin acetate (TPTA). KAPAS activity was completely inhibited by TPTA with an IC50 of 19.85 μM. 40-day-old Arabidopsis thaliana plants were killed with foliar treatment of 125 g ha-1 TPTA under the greenhouse conditions. The germination of A. thaliana seeds was also completely inhibited with 62.5 μM TPTA, but it was rescued to 85-92% with the supplement of biotin biosynthesis intermediates such as 0.5 mM of biotin, dethiobiotin, and 7,8-diaminopelargonic acid, but not by 7-keto-8-aminopelargonic acid (KAPA). However, additional supplement of 0.5 mM S-adenosyl-l-methionine (SAM) with 0.5 mM KAPA rescued up to 91% of the germination previously inhibited by the 50 μM TPTA. Also, biotin supplements alleviated the growth inhibition of 40-day-old A. thaliana plant. Foliar application of TPTA induced 8-fold higher substrate (l-alanine) accumulation in the treated A. thaliana plants. RNA expression for KAPAS transcripts were much fainter in the lane representing leaf tissue treated with TPTA. With these results, we report that SAM is an essential donor of amino groups for synthesis of the biotin precursor KAPA to 7,8-diaminopelargonic acid (DAPA) synthesis in plants, that KAPAS is a potential herbicidal target site in the biotin biosynthesis pathway, and that TPTA might be one of the potential KAPAS inhibitors. © 2009 Elsevier Inc. All rights reserved.

Kim D.S.,Genomine Inc. | Choi Y.D.,Yonsei University | Moon M.,Genomine Inc. | Kang S.,Yonsei University | And 4 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2013

Background: Early detection of renal cell carcinoma using serum/plasma biomarkers remains challenging. To validate clinical performance of potential candidate markers for kidney tumors, three-marker assay composed of nicotinamide N-methyltransferase (NNMT), L-plastin (LCP1), and nonmetastatic cells 1 protein (NM23A) was evaluated. Methods: Patients with kidney cancer and control group were included in the clinical evaluation. Participants were divided into cohorts representing the training group of control group including healthy and benign tumors (n 102) and patients with kidney cancer (n 87) that were used to identify criteria for scoring. Then, we developed a three-marker assay that was validated with a cohort of test group samples (n 100). A scoring method based on the cut-point of each of the three markers was used to evaluate the diagnostic performance of the marker combination. Results: Plasma levels of NNMT, LCP1, and NM23A were highly elevated in patients with kidney cancer (P < 0.0001). In 289 blind sample tests with control subjects (n 175) and patients with kidney cancer (n 114), the diagnostic accuracy of NNMT alone and the three-marker assay was 0.913 and 0.932, respectively. When 90% specificity was defined, the sensitivity of NNMT and the three-marker assay was 71.9% and 95.7%, respectively. The predictive value of the three-marker assay was 87.2% (+PPV) and 97% (PPV). Conclusions: The composite assay with NNMT, LCP1, and NM23A was a promising novel serum marker assay for the early detection of malignant kidney tumors covering subtypes of RCC with high diagnostic characteristics. Impact: NNMT/LCP1/NM23A triple markers could be a helpful screening assay to detect early RCC. © 2013 American Association for Cancer Research.

Lee D.H.,Genomine Inc. | Lee I.C.,Daegu Gyeongbuk Institute of Science and Technology | Kim K.J.,Genomine Inc. | Kim D.S.,Genomine Inc. | And 6 more authors.
Journal of Plant Biology | Year: 2014

Gibberellin (GA), a plant hormone, is involved in many aspects of plant growth and development both in vegetative and reproductive phases. GA2-oxidase plays a key role in the GA catabolic pathway to reduce bioactive GAs. We produced transgenic Arabidopsis plants expressing GA2-oxidase 4 (AtGA2ox4) under the control of a senescenceassociated promoter (SEN1). As we hypothesized, transgenic plants (SEN1::AtGA2ox4) exhibited a dominant semi-dwarf phenotype with a decrease of bioactive GAs (e.g., GA4 and GA1) up to two-fold compared to control plants. Application of bioactive GA3 resulted in increased shoot length, indicating that the GA signaling pathway functions normally in the SEN1::AtGA2ox4 plants. Expressions of other members of GA2-oxidase family, such as AtGA2ox1, AtGA2ox3, AtGA2ox6, and AtGA2ox8, were decreased slightly in the flower and silique tissues while GA biosynthetic genes (e.g., AtGA20ox1, AtGA20ox2 and AtGA3ox1) were not significantly changed in the SEN::AtGA2ox4 plants. Using proteome profiling (2-D PAGE followed by MALDI-TOF/MS), we identified 29 protein spots that were increased in the SEN1::AtGA2ox4 plants, but were decreased to wild-type levels by GA3 treatment. The majority were found to be involved in photosynthesis and carbon/energy metabolism. Unlike the previous constitutive over-expression of GA2-oxidases, which frequently led to floral deformity and/or loss of fertility, the SEN1::AtGA2ox4 plants retained normal floral morphology and seed production. Accordingly, the expressions of FT and CO genes remained unchanged in the SEN1::AtGA2ox4 plants. Taken together, our results suggest that the dominant dwarf trait carried by SEN1::AtGA2ox4 plants can be used as an efficient dwarfing tool in plant biotechnological applications. © 2014 Korean Society of Plant Biologists and Springer-Verlag Berlin Heidelberg.

Genomine Inc. | Date: 2015-07-15

The present invention provides a method and a kit for detecting renal cancer blood biomarkers. More particularly, the present invention relates to a method and a kit for detecting all of NNMT, LCP1 and NM23A, which are renal cancer blood biomarkers. The result of the detection may be effectively used in determining whether renal cancer has been contracted, the stages of renal cancer and the treatment progress of renal cancer by a medical specialist such as a doctor or the like. In particular, the result of the detection may be effectively used in the early diagnosis of renal cancer and the diagnosis of clear cell type renal cell carcinoma which constitutes the majority of types of renal cell carcinoma.

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