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Muralidharan Mani, Unn Hwa Lee, Nal Ae Yoon, Eun Hye Yoon, Byung Ju Lee, Wha Ja Cho, Jeong Woo Park
Previously we have reported that developmentally regulated GTP-binding protein 2 (DRG2) localizes on Rab5 endosomes and plays an important role in transferrin (Tfn) recycling. We here identified DRG2 as a key regulator of membrane tubule stability. At 30 min after Tfn treatment, DRG2 localized to membrane tubules which were enriched with phosphatidylinositol 4-monophosphate [PI(4)P] and did not contain Rab5. DRG2 interacted with Rac1 more strongly with GTP-bound Rac1 and tubular localization of DRG2 depended on Rac1 activity...
November 4, 2017: Biochemical and Biophysical Research Communications
S Shuib, N N Saaid, Z Zakaria, J Ismail, Z Abdul Latiff
Potocki-Lupski syndrome (PTLS), also known as duplication 17p11.2 syndrome, trisomy 17p11.2 or dup(17)(p11.2p11.2) syndrome, is a developmental disorder and a rare contiguous gene syndrome affecting 1 in 20,000 live births. Among the key features of such patients are autism spectrum disorder, learning disabilities, developmental delay, attention-deficit disorder, infantile hypotonia and cardiovascular abnormalities. Previous studies using microarray identified variations in the size and extent of the duplicated region of chromosome 17p11...
April 2017: Malaysian Journal of Pathology
Mai-Tram Vo, Myoung Seok Ko, Unn Hwa Lee, Eun Hye Yoon, Byung Ju Lee, Wha Ja Cho, Chang Man Ha, Kyungjin Kim, Jeong Woo Park
Mitochondrial dynamics, including constant fusion and fission, play critical roles in maintaining mitochondrial morphology and function. Here, we report that developmentally regulated GTP-binding protein 2 (DRG2) regulates mitochondrial morphology by modulating the expression of the mitochondrial fission gene dynamin-related protein 1 (Drp1). shRNA-mediated silencing of DRG2 induced mitochondrial swelling, whereas expression of an shRNA-resistant version of DRG2 decreased mitochondrial swelling in DRG2-depleted cells...
May 13, 2017: Biochemical and Biophysical Research Communications
Soo Hwa Jang, Ah-Ram Kim, Neung-Hwa Park, Jeong Woo Park, In-Seob Han
Developmentally regulated GTP-binding protein 2 (DRG2) plays an important role in cell growth. Here we explored the linkage between DRG2 and G2/M phase checkpoint function in cell cycle progression. We observed that knockdown of DRG2 in HeLa cells affected growth in a wound-healing assay, and tumorigenicity in nude mice xenografts. Flow cytometry assays and [(3)H] incorporation assays indicated that G2/M phase arrest was responsible for the decreased proliferation of these cells. Knockdown of DRG2 elicited down-regulation of the major mitotic promoting factor, the cyclin B1/Cdk1 complex, but up-regulation of the cell cycle arresting proteins, Wee1, Myt1, and p21...
September 2016: Molecules and Cells
Muralidharan Mani, Unn Hwa Lee, Nal Ae Yoon, Hyo Jeong Kim, Myoung Seok Ko, Wongi Seol, Yeonsoo Joe, Hun Taeg Chung, Byung Ju Lee, Chang Hoon Moon, Wha Ja Cho, Jeong Woo Park
The small GTPase Rab5 regulates the early endocytic pathway of transferrin (Tfn), and Rab5 deactivation is required for Tfn recycling. Rab5 deactivation is achieved by RabGAP5, a GTPase-activating protein, on the endosomes. Here we report that recruitment of RabGAP5 is insufficient to deactivate Rab5 and that developmentally regulated GTP-binding protein 2 (DRG2) is required for Rab5 deactivation and Tfn recycling. DRG2 was associated with phosphatidylinositol 3-phosphate-containing endosomes. It colocalized and interacted with EEA1 and Rab5 on endosomes in a phosphatidylinositol 3-kinase-dependent manner...
January 15, 2016: Molecular Biology of the Cell
Myoung Seok Ko, Hyo Jeong Kim, Hong Kyung Kim, Nal Ae Yoon, Unn Hwa Lee, Sang Chul Lee, Dae Kyun Chung, Byung Ju Lee, Jae Hee Suh, Wha Ja Cho, Jeong Woo Park
Developmentally regulated GTP-binding protein 2 (DRG2) represents a novel subclass of GTP-binding proteins. We here report that transgenic overexpression of DRG2 in mice ameliorates experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). The protective effect of DRG2 in EAE was mediated by the inhibition of the development of T(H)17 cells. DRG2 enhanced the activity of PPARγ, which led to an inhibition of the nuclear factor kappa B (NF-κB) activity and IL-6 production in antigen presenting cells and an inhibition of the development of T(H)17 cells...
February 2014: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Kosuke Ishikawa, Koichi Ito, Jun-ichiro Inoue, Kentaro Semba
The molecular fine-tuning mechanisms underlying adaptive responses to environmental stresses in eukaryotes remain largely unknown. Here, we report on a novel stress-induced cell growth control mechanism involving a highly conserved complex containing Rbg2 and Gir2 subunits, which are the budding yeast orthologs of human Drg2 and Dfrp2, respectively. We found that the complex is responsible for efficient cell growth under amino acid starvation. Using native PAGE analyses, we observed that, individually, Rbg2 and Gir2 were labile proteins...
October 2013: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Guang-dong Tong, Xi Zhang, Da-qiao Zhou, Chun-shan Wei, Jin-song He, Chun-ling Xiao, Xin-liang Liu, Ying-jun Zheng, Si-nuan Chen, Hai-hong Tang
OBJECTIVE: To observe the change in the number of antibodies of preneoplastic hepatocellular carcinoma (HCC) using early treatment by Compound Phyllanthus Urinaria L. (CPUL) on patients with preneoplastic hepatitis B virus (HBV)-associated HCC. METHODS: A total of 102 cirrhosis patients with regenerative or dysplastic nodules whose sera were tested positive for at least one of these six proteins (five up-regulated genes URG4, URG7, URG11, URG12 and URG19, and one down-regulated gene DRG2) were assigned randomly to two groups using continual random codes by SPSS software...
April 2014: Chinese Journal of Integrative Medicine
Ke Ke, Ok-Joo Sul, Woon-Ki Kim, Mi-Hyun Lee, Myung-Seok Ko, Jae-Hee Suh, Hyun-Ju Kim, Shin-Yoon Kim, Jeong-Woo Park, Hye-Seon Choi
The developmentally regulated GTP-binding protein-2 (DRG2) is a novel subclass of GTP-binding proteins. Many functional characteristics of osteoclasts (OC) are associated with small GTPases. We hypothesized that DRG2 affects bone mass via modulating OC activity. Using DRG2 transgenic mice, we investigated the role of DRG2 in bone remodeling. DRG2 overexpression caused a decrease in bone mass and an increase in the number and activity of OC in vivo. DRG2 overexpression increased fusion, spreading, survival, and resorption activity of OC in vitro...
April 1, 2013: American Journal of Physiology. Endocrinology and Metabolism
Jie Chen, Bai-Yong Shen, Xia-Xing Deng, Qian Zhan, Cheng-Hong Peng
Developmentally regulated GTP-binding protein 2 (DRG2), an evolutionarily conserved member of the DRG subfamily in the GTP-binding protein, is thought to play an essential role in the control of cell growth and differentiation. However, the role of DRG2 in hepatocellular carcinoma cells is largely unknown. Here, we show that DRG2 is down-regulated during chemotherapeutic drug induced apoptosis in four hepatocellular carcinoma cell lines. We further provided evidence that DRG2 was a substrate of a SKP1-CULLIN1-F-box E3 ligase complex and inhibition the function of Cullin1 prevented the degradation of DRG2 during apoptosis...
April 13, 2012: Biochemical and Biophysical Research Communications
Hyo Jeong Kim, Myoung Seok Ko, Hong Kyung Kim, Wha Ja Cho, Seon Ho Lee, Byung Ju Lee, Jeong Woo Park
Developmentally regulated GTP-binding protein 2 (DRG2) is an evolutionarily conserved GTP-binding protein. DRG2 mRNA expression has been confirmed in many animal and human tissues. DRG2 is thought to play an essential role in the control of cell growth and differentiation. However, transcriptional regulation of DRG2 is largely unknown. To investigate the mechanisms controlling DRG2 expression, we cloned 1509bp of the 5'-flanking sequence of this gene. Deletion analysis showed that the region between -113 and -70 is essential for the basal level expression of the DRG2 gene in K562 human erythroleukemic cells...
March 2011: Biochimica et Biophysica Acta
Weizhang Wang, Biyu Zhang, Hongyuan Chen, Li Zhang
To study the anticancer activities of curcumin on human hepatocarcinoma cell line Sk-hep-1 and its related molecular mechanism which has not been elucidated. In the present study,we showed that curcumin inhibited proliferation of Sk-hep-1 cells in a dose-dependent manner through MTF assay. The effect of curcumin on apoptosis in Sk-hep-1 cells was investigated by DAPI staining and the various apoptosis was observed in hepatocarcinoma cell lines Sk-hep-1, HepG2 and Hep3B, but not in normal liver cell line Chang's liver with curcumin treatment...
February 2010: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Kosuke Ishikawa, Taishin Akiyama, Koichi Ito, Kentaro Semba, Jun-ichiro Inoue
Various widely known GTPases are associated with diverse crucial cellular processes. However, the functional targets of the universally conserved homologous GTPases Drg1 and Drg2, constituting the DRG subfamily in eukaryotes, remain completely unknown despite their pleiotropic cell growth effects. Contrary to expectations of functional redundancy between Drg1 and Drg2 due to their high homology, the different binding proteins Dfrp1 and Dfrp2, respectively, have been previously identified. Here, we report the first systematic characterization of all these proteins in mammals by analyses in physiological conditions...
December 18, 2009: Biochemical and Biophysical Research Communications
Anthony O'Connell, Gautier Robin, Bostjan Kobe, José Ramón Botella
Developmentally regulated G-proteins (DRGs) are a highly conserved family of GTP-binding proteins found in archaea, plants, fungi and animals, indicating important roles in fundamental pathways. Their function is poorly understood, but they have been implicated in cell division, proliferation, and growth, as well as several medical conditions. Individual subfamilies within the G-protein superfamily possess unique nucleotide binding and hydrolysis rates that are intrinsic to their cellular function, and so characterization of these rates for a particular G-protein may provide insight into its cellular activity...
October 2009: Protein Expression and Purification
Alisa Nakamine, Leonid Ouchanov, Patricia Jiménez, Elina R Manghi, Marcela Esquivel, Silvia Monge, Marietha Fallas, Barbara K Burton, Barbara Szomju, Sarah H Elsea, Christian R Marshall, Stephen W Scherer, L Alison McInnes
Duplications of 17(p11.2p11.2) have been associated with various behavioral manifestations including attention deficits, obsessive-compulsive symptoms, autistic traits, and language delay. We are conducting a genetic study of autism and are screening all cases for submicroscopic chromosomal abnormalities, in addition to standard karyotyping, and fragile X testing. Using array-based comparative genomic hybridization analysis of data from the Affymetrix GeneChip(R) Human Mapping Array set, we detected a duplication of approximately 3...
March 1, 2008: American Journal of Medical Genetics. Part A
Kosuke Ishikawa, Sakura Azuma, Shuntaro Ikawa, Kentaro Semba, Jun-ichiro Inoue
DRG1 and DRG2 comprise a highly conserved subfamily of GTP-binding proteins and are thought to act as critical regulators of cell growth. Their abnormal expressions may trigger cell transformation or cell cycle arrest. Our aim is to clarify their physiological functions and regulatory mechanisms. Here we report identification of novel proteins, DRG family regulatory protein (DFRP) 1 and DFRP2, which regulate expression of DRG proteins through specific binding. In transient transfection experiments, DFRP1 specifically binds DRG1, and DFRP2 preferentially binds DRG2...
February 2005: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Federico del Río-Portilla, Elizabeth Hernández-Marín, Genaro Pimienta, Fredy V Coronas, Fernando Z Zamudio, Ricardo C Rodríguez de la Vega, Enzo Wanke, Lourival D Possani
Cn12 isolated from the venom of the scorpion Centruroides noxius has 67 amino-acid residues, closely packed with four disulfide bridges. Its primary structure and disulfide bridges were determined. Cn12 is not lethal to mammals and arthropods in vivo at doses up to 100 microg per animal. Its 3D structure was determined by proton NMR using 850 distance constraints, 36 phi angles derived from 36 coupling constants obtained by two different methods, and 22 hydrogen bonds. The overall structure has a two and half turn alpha-helix (residues 24-32), three strands of antiparallel beta-sheet (residues 2-4, 37-40 and 45-48), and a type II turn (residues 41-44)...
June 2004: European Journal of Biochemistry
Hebok Song, Sin-Il Kim, Myoung Seok Ko, Hyo Jeong Kim, Jin Chul Heo, Hae Jin Lee, Han Saem Lee, In Seob Han, KyuBum Kwack, Jeong Woo Park
DRG2, a member of the DRG subfamily in the GTP-binding protein superfamily, was identified as a repressed gene product in fibroblasts transformed by SV40. The significance of this down-regulation and the cellular role of DRG2 has not been understood in the past. To investigate the function of DRG2 we made a Jurkat cell line, Jurkat-LNCX2-DRG2, stably transfected with pLNCX2-DRG2 to overexpress human DRG2. Cell cycle distribution analysis revealed an increased accumulation of G(2)/M phase cells in Jurkat-LNCX2-DRG2 cells, indicating a retardation of cell-cycle progression...
March 2004: Journal of Biochemistry
Myoung Seok Ko, Unn Hwa Lee, Sin Il Kim, Hyo Jeong Kim, Jeong Jae Park, Seung Ju Cha, Sung Bum Kim, Hebok Song, Dae Kyun Chung, In Seob Han, KyuBum Kwack, Jeong Woo Park
Developmentally regulated GTP-binding protein (DRG) is a new subfamily within the superfamily of GTP-binding proteins. Its expression is regulated during embryonic development. To investigate the effect of the expression of DRG2 on cell growth, we constructed a human Jurkat-T-cell line that overexpresses DRG2. Overexpression of DRG2 suppressed the growth and the aggregation of Jurkat cells but did not induce apoptotic cell death. We used cDNA microarray analysis to examine the global changes in gene expression induced by an overexpression of DRG2...
February 15, 2004: Archives of Biochemistry and Biophysics
Kosuke Ishikawa, Sakura Azuma, Shuntaro Ikawa, Yasuyuki Morishita, Jin Gohda, Taishin Akiyama, Kentaro Semba, Jun ichiro Inoue
The developmentally regulated GTP-binding protein (DRG) subfamily is an uncharacterized member of the Obg family, an evolutional branch of GTPase superfamily proteins. GTPases act as molecular switches regulating diverse cellular processes. DRG2 and DRG1 comprise the DRG subfamily in eucaryotes. Although drg1 was first identified as a gene predominantly expressed during early development of the mouse central nervous system, comparative analysis of drg2 and drg1 expression during embryogenesis has never been reported, and the biochemical properties of the DRG family proteins remain to be elucidated...
December 11, 2003: Gene
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