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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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Korean Society for Biochemistry and Molecular Biology
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Volume & Issues
Volume 42, Issue 12 - Dec 2009
Volume 42, Issue 11 - Nov 2009
Volume 42, Issue 10 - Oct 2009
Volume 42, Issue 9 - Sep 2009
Volume 42, Issue 8 - Aug 2009
Volume 42, Issue 7 - Jul 2009
Volume 42, Issue 6 - Jun 2009
Volume 42, Issue 5 - May 2009
Volume 42, Issue 4 - Apr 2009
Volume 42, Issue 3 - Mar 2009
Volume 42, Issue 2 - Feb 2009
Volume 42, Issue 1 - Jan 2009
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The Hsp90 chaperone machinery: from structure to drug development
Hahn, Ji-Sook ;
BMB Reports , volume 42, issue 10, 2009, Pages 623~630
DOI : 10.5483/BMBRep.2009.42.10.623
Hsp90, an evolutionarily conserved molecular chaperone, is involved in the folding, stabilization, activation, and assembly of a wide range of 'client' proteins, thus playing a central role in many biological processes. Especially, several oncoproteins act as Hsp90 client proteins and tumor cells require higher Hsp90 activity than normal cells to maintain their malignancy. For this reason, Hsp90 has emerged as a promising target for anti-cancer drug development. It is still largely unknown how Hsp90 can recognize structurally unrelated client proteins. However, recent progress in structural studies on Hsp90 and its interaction with various co-chaperones has broadened our knowledge of how the Hsp90 ATPase activity, which is essential for its chaperone function, is regulated and coupled with the conformational changes of Hsp90 dimer. This review focuses on the roles of various Hsp90 co-chaperones in the regulation of the Hsp90 ATPase cycle, as well as in the selection of client proteins. In addition, the current development of Hsp90 inhibitors based on the structural information will be discussed.
Heat shock transcription factors and sensory placode development
Nakai, Akira ;
BMB Reports , volume 42, issue 10, 2009, Pages 631~635
DOI : 10.5483/BMBRep.2009.42.10.631
The heat shock transcription factor (HSF) family consists of at least three members in mammals and regulates expression of heat shock proteins in response to heat shock and proteotoxic stresses. Especially, HSF1 is indispensable for this response. Members of this family are also involved in development of some tissues such as the brain and reproductive organs. However, we did not know the molecular mechanisms that regulate developmental processes. Involvement of HSFs in the sensory development was implicated by the finding that human hereditary cataract is associated with mutations of the HSF4 gene. Analysis of gene-disrupted mice showed that HSF4 and HSF1 are required for the lens and the olfactory epithelium, respectively. Furthermore, a common molecular mechanism that regulates developmental processes was revealed by analyzing roles of HSFs in the two developmentally-related organs.
Development and characterization of a fully functional small anti-HER2 antibody
Gao, Jie ; Li, Bohua ; Li, Huimei ; Zhang, Xunmin ; Zhang, Dapeng ; Zhao, Lei ; Wang, Chong ; Fang, Chen ; Qian, Weizhu ; Hou, Sheng ; Kou, Geng ; Wei, Huafeng ; Shi, Shu ; Wang, Hao ; Guo, Yajun ;
BMB Reports , volume 42, issue 10, 2009, Pages 636~641
DOI : 10.5483/BMBRep.2009.42.10.636
The penetrating of monoclonal antibodies (mAbs) into solid tumor may be hampered by their large size. The antibody mimetics, composed of two complementarity-determining regions (CDRs) through a cognate framework region (FR), have been demonstrated to have the capacity to penetrate tumors superior to its parental intact IgG. In this study, we used CDR and FR sequences from the humanized anti-HER2 monoclonal antibody trastuzumab to design four antibody mimetics. Then these antibody mimetics were fused to human IgG Fc to generate mimetics-Fc small antibodies. One of the four mimetics-Fc antibodies binds well to HER2-overexpressing SK-BR3 cells and effectively inhibits the binding of trastuzumab. This mimetics-Fc, denoted as HMTI-Fc, was shown to be effective in mediating antibody-dependent cellular cytotoxicity and exhibit an antiproliferative effect in SK-BR3 cells. To our knowledge, the HMTI-Fc antibody shown here is the smallest fully functional antibody and may have a potential for treatment of cancer.
The opposite correlation between calcium ion and cyclic-AMP regarding the activation of microsomal triglyceride transfer protein in rat liver
Cho, Hyun-Jeong ; Kim, Hyeong-Soo ; Yu, Young-Bin ; Kang, Hyo-Chan ; Lee, Dong-Ha ; Rhee, Man-Hee ; Cho, Jae-Youl ; Park, Hwa-Jin ;
BMB Reports , volume 42, issue 10, 2009, Pages 642~647
DOI : 10.5483/BMBRep.2009.42.10.642
In this study, the effects of
and cyclic adenosine monophosphate (cAMP) on microsomal triglyceride (TG) transfer protein (MTP) activity were investigated in rat liver. MTP activity was high when liver contained low levels of cAMP, which was induced by administration of glucose, or high levels of total
and TG. However, MTP activity increased by high levels of
and TG was reduced in a dose-dependent manner by treatment with dibutyryl-cAMP (db-cAMP), a cAMP analogue. Conversely, when homogenates of liver from normal rats, with low levels of total
and high levels of cAMP, were incubated with thapsigargin, a
-inducer, MTP activity was increased in a dose-dependent manner compared to control. Therefore, our results suggest that high levels of
cause hypertriglyceridemia through the elevation of MTP activity, as opposed to high levels of cAMP, which suppress MTP activity and inhibit hypertriglyceridemia.
Radish phospholipid hydroperoxide glutathione peroxidase provides protection against hydroperoxide-mediated injury in mouse 3T3 fibroblasts
Li, Tian ; Liu, Guan-Lan ; Duan, Ming-Xing ; Liu, Jin-Yuan ;
BMB Reports , volume 42, issue 10, 2009, Pages 648~654
DOI : 10.5483/BMBRep.2009.42.10.648
Overexpression of phospholipid hydroperoxide glutathione peroxidase (PHGPx) genes has been reported to play an important role in protecting host cells from oxidative injury in several model systems. A radish phospholipid hydroperoxide glutathione peroxidase (RsPHGPx) known to have high catalytic activity was applied to mouse 3T3 fibroblasts to determine the protective effects of PHGPx against oxidative injury triggered by hydroperoxides such as hydrogen peroxide (
), tert-butyl hydroperoxide (t-BHP) and phosphatidylcholine hydroperoxide (PCOOH). We observed that preincubation of cells with RsPHGPx significantly increased cell viability, reduced levels of malondialdehyde (MDA), inhibited generation of reactive oxygen species (ROS), and maintained natural cell shapes after treatment with
, t-BHP or PCOOH, indicating that the exogenous RsPHGPx can act as an effective hydroperoxide-scavenger and may also protect target cells from oxidative damage. These results suggest the possibility for use of RsPHGPx as a therapeutic protectant.
Anti-invasive activity of histone deacetylase inhibitors via the induction of Egr-1 and the modulation of tight junction-related proteins in human hepatocarcinoma cells
Kim, Sung-Ok ; Choi, Byung-Tae ; Choi, Il-Whan ; Cheong, Jae-Hun ; Kim, Gi-Young ; Kwon, Taeg-Kyu ; Kim, Nam-Deuk ; Choi, Yung-Hyun ;
BMB Reports , volume 42, issue 10, 2009, Pages 655~660
DOI : 10.5483/BMBRep.2009.42.10.655
The potential anti-metastasis and anti-invasion activities of early growth response gene-1 (Egr-1) and claudin-3, a tight junction (TJ)-related protein, were evaluated using histone deacetylase (HDAC) inhibitors in human hepatocarcinoma cells. The results of wound healing and Transwell assays showed that HDAC inhibitors such as trichostatin A and sodium butyrate inhibited cell migration and invasion. HDAC inhibitors markedly induced Egr-1 expression during the early period, after which expression levels decreased. In addition, the down-regulation of snail and type 1 insulin-like growth factor receptor (IGF-1R) in HDAC inhibitor- treated cells induced the upregulation of thrombospondin-1 (TSP-1), E-cadherin and claudin-3. Cells transfected with Egr-1 and claudin-3 siRNA displayed significant blockage of HDAC inhibitor-induced anti-invasive activity. Collectively, these findings indicate that the up-regulation of Egr-1 and claudin-3 are crucial steps in HDAC inhibitor-induced anti-metastasis and anti-invasion.
Proteomic analysis of porcine pancreas development
Choi, Jong-Soon ; Cho, Young-Keun ; Yoon, Sung-Ho ; Kwon, Sang-Oh ; Koo, Deog-Bon ; Yu, Kweon ;
BMB Reports , volume 42, issue 10, 2009, Pages 661~666
DOI : 10.5483/BMBRep.2009.42.10.661
Porcine pancreas development is not well studied at the molecular level despite being a therapeutic resource for diabetic patients. In this study, we investigated expression of lineage markers and performed proteomic analysis. Expression of the early lineage markers Pdx1 and Ptf1a was developmentally conserved between mice and pigs, whereas expression of the islet differentiation marker Pax4 was delayed in porcine compared with murine pancreas development. Proteomic analysis found that expression levels of chymotrypsinogen were down-regulated during porcine pancreas development while those of digestive enzymes like lipases, elastase and serine protease were up-regulated. In addition, specific isoforms of protein folding assistants such as protein disulfide isomerase and prefoldin were expressed at specific stages during the maturation of digestive enzymes. Taken together, these results show that development of the porcine pancreas is regulated by a concerted interplay of pancreas lineage marker proteins and other specified proteins, resulting in a functional endocrine and exocrine organ.
Lipid accumulation mediated by adiponectin in C2C12 myogenesis
Yin, Changjun ; Long, Qinqiang ; Lei, Ting ; Chen, Xiaodong ; Long, Huan ; Feng, Bin ; Peng, Yin ; Wu, Yanling ; Yang, Zaiqing ;
BMB Reports , volume 42, issue 10, 2009, Pages 667~672
DOI : 10.5483/BMBRep.2009.42.10.667
Plasma concentrations of adiponectin have been shown to be decreased in patients with obesity, cardiovascular diseases, hypertension and metabolic syndrome. Recent studies have found that adiponectin reduces lipid accumulation in macrophage foam cells which may impact the development of atherosclerosis. However, it remains unclear whether adiponectin is involved in the process of lipid accumulation during myogenesis. Using C2C12 myoblasts, we investigated the effect of adiponectin on intramyocellular lipid accumulation during myogenesis. The results showed that intracellular lipid accumulation is significantly decreased during C2C12 differentiation, apparently due to increased fatty acid oxidation and decreased fatty acid synthesis during this process. C2C12 cells transiently transfected with adiponectin gene showed reduced lipid accumulation as compared to controls. Further experiments demonstrated that adiponectin can suppress lipid accumulation by increasing fatty acid oxidation during C2C12 myogenesis.
Isolation and characterization of a novel short-chain alcohol dehydrogenase gene from Panax ginseng
Kim, Yu-Jin ; Shim, Ju-Sun ; Lee, Jung-Hye ; Jung, Dae-Young ; Sun, Hwa ; In, Jun-Gyo ; Yang, Deok-Chun ;
BMB Reports , volume 42, issue 10, 2009, Pages 673~678
DOI : 10.5483/BMBRep.2009.42.10.673
The cDNA of alcohol dehydrogenase (PgADH) was isolated and characterized from the leaf of Panax ginseng. The cDNA had an open reading frame of 801 bp and a deduced amino acid sequence of 266 residues. The calculated molecular mass of the mature protein is approximately 29 kDa with a predicated isoelectric point of 6.84. Homology analysis revealed that the deduced amino acid of PgADH shares a high degree of homology with the short-chain ADH proteins of other plants. Genomic DNA hybridization analysis indicated that PgADH represents a multi-gene family. The expression of PgADH under various environmental stresses was analyzed at different time points using real-time PCR. ABA, SA and especially JA (80-fold) significantly induced PgADH expression within 24 h of treatment. The positive responses of PgADH to abiotic stimuli suggest that ginseng ADH may protect against hormone-related environmental stresses.
Fenofibrate reduces adiposity in pregnant and virgin rats but through different mechanisms
Del Carmen Gonzalez, Maria ; Vidal, Hubert ; Herrera, Emilio ; Bocos, Carlos ;
BMB Reports , volume 42, issue 10, 2009, Pages 679~684
DOI : 10.5483/BMBRep.2009.42.10.679
Fenofibrate has been proven to reduce adiposity. Since gestation produces an increase in white adipose tissue (WAT) mass, we comparatively studied this drug-effect in virgin and pregnant rats. Fenofibrate reduced lumbar WAT weight in both pregnant and virgin rats. Fenofibrate treatment did not modify plasma free fatty acid (FFA) concentration in virgin rats, it greatly increased it in pregnant animals. Remarkable differences between the two groups were obtained for two proteins related to fatty acid oxidation and esterification and storing. Respectively, the mRNA levels of carnitine palmitoyltransferase I (CPT-I) were increased by the fenofibrate only in the virgin rats and a similar finding was observed for the expression of phosphoenolpyruvate carboxykinase (PEPCK). These findings indicate that fenofibrate reduces adiposity in pregnant and virgin rats through different mechanisms: a) in virgin rats, by promoting fatty acid oxidation; and b) in pregnant rats, by enhancing fatty acid output.
Sphingosine 1-phosphate induces vesicular endothelial growth factor expression in endothelial cells
Heo, Kyun ; Park, Kyung-A ; Kim, Yun-Hee ; Kim, Sun-Hee ; Oh, Yong-Seok ; Kim, In-Hoo ; Ryu, Sung-Ho ; Suh, Pann-Ghill ;
BMB Reports , volume 42, issue 10, 2009, Pages 685~690
DOI : 10.5483/BMBRep.2009.42.10.685
Angiogenesis is essential for tumor growth and vascular endothelial cell growth factor (VEGF) plays a key role in this process. Conversely, sphingosine 1-phosphate (S1P) is a biologically active sphingolipid known to play a key role in cancer progression by regulating endothelial cell proliferation and migration. In this study, the authors found that S1P increases the level of VEGF mRNA in human umbilical vein endothelial cells (HUVECs) and immortalized HUVECs (iHUVECs). Additionally, S1P was found to increase VEGF promoter activity in MS-1 mouse pancreatic islet endothelial cells. Furthermore, a pharmacological inhibitory study revealed that
-mediated phospholipase C, Akt, Erk, and p38 MAPK signaling are involved in this S1P-induced expression of VEGF. A component of AP1 transcription factor is important for S1P-induced VEGF expression. Taken together, these findings suggest that S1P enhances endothelial cell proliferation and migrat ion by upregulating the expression of VEGF mRNA.
Transcriptional activation of pref-1 by E2F1 in 3T3 L1 cells
Shen, Yan-Nan ; Kim, Yoon-Mo ; Yun, Cheol-Heui ; Moon, Yang-Soo ; Kim, Sang-Hoon ;
BMB Reports , volume 42, issue 10, 2009, Pages 691~696
DOI : 10.5483/BMBRep.2009.42.10.691
The E2F gene family appears to regulate the proliferation and differentiation of events that are required for adipogenesis. Pref-1 is a transmembrane protein that inhibits adipocyte differentiation in 3T3-L1 cells. In this study, we found that the expression of pref-1 is regulated by the transcription factor E2F1. The expression of pref-1 and E2F1 was strongly induced in preadipocytes and at the late differentiation stage. Using luciferase reporter assay, ChIP assay and EMSA, we found that the -211/-194 region of the pref-1 promoter is essential for the binding of E2F1 as well as E2F1-dependent transcriptional activation. Knockdown of E2F1 reduced both pref-1 promoter activity and the level of pref-1 mRNA. Taken together, our data suggest that transcriptional activation of pref-1 is stimulated by E2F1 protein in adipocytes.