The Experts below are selected from a list of 303 Experts worldwide ranked by ideXlab platform
Karsten Rippe - One of the best experts on this subject based on the ideXlab platform.
-
Human ISWI chromatin-remodeling complexes sample nucleosomes via transient binding reactions and become immobilized at active sites
Proceedings of the National Academy of Sciences of the United States of America, 2010Co-Authors: Fabian Erdel, Thomas Schubert, Caroline Marth, Gernot Längst, Karsten RippeAbstract:Chromatin remodeling complexes can translocate nucleosomes along the DNA in an ATP-dependent manner. Here, we studied autofluorescent protein constructs of the human ISWI family members Snf2H, Snf2L, the catalytically inactive Snf2L+13 splice variant, and the accessory Acf1 subunit in living human and mouse Cells by fluorescence microscopy/spectroscopy. Except for Snf2L, which was not detected in the U2OS Cell Line, the endogenous ISWI proteins were abundant at nuclear concentrations between 0.14 and 0.83 μM. A protein interaction analysis showed the association of multimeric Snf2H and Acf1 into a heterotetramer or higher-order ACF complex. During the G1/2 Cell cycle phase, Snf2H and Snf2L displayed average residence times
-
Dynamics of Telomeres and Promyelocytic Leukemia Nuclear Bodies in a Telomerase-negative Human Cell Line
Molecular biology of the cell, 2009Co-Authors: Thibaud Jegou, Inn Chung, Gerrit Heuvelman, Malte Wachsmuth, Sabine M. Görisch, Karin M. Greulich-bode, Petra Boukamp, Peter Lichter, Karsten RippeAbstract:Telomerase-negative tumor Cells maintain their telomeres via an alternative lengthening of telomeres (ALT) mechanism. This process involves the association of telomeres with promyelocytic leukemia nuclear bodies (PML-NBs). Here, the mobility of both telomeres and PML-NBs as well as their interactions were studied in human U2OS osteosarcoma Cells, in which the ALT pathway is active. A U2OS Cell Line was constructed that had lac operator repeats stably integrated adjacent to the telomeres of chromosomes 6q, 11p, and 12q. By fluorescence microscopy of autofluorescent LacI repressor bound to the lacO arrays the telomere mobility during interphase was traced and correlated with the telomere repeat length. A confined diffusion model was derived that describes telomere dynamics in the nucleus on the time scale from seconds to hours. Two telomere groups were identified that differed with respect to the nuclear space accessible to them. Furthermore, translocations of PML-NBs relative to telomeres and their complexes with telomeres were evaluated. Based on these studies, a model is proposed in which the shortening of telomeres results in an increased mobility that could facilitate the formation of complexes between telomeres and PML-NBs.
Paul R Thompson - One of the best experts on this subject based on the ideXlab platform.
-
design synthesis and biological evaluation of tetrazole analogs of cl amidine as protein arginine deiminase inhibitors
Journal of Medicinal Chemistry, 2015Co-Authors: Venkataraman Subramanian, Jason S Knight, Sangram S Parelkar, Lynne J Anguish, Scott A Coonrod, Mariana J Kaplan, Paul R ThompsonAbstract:Protein arginine deiminases (PADs) catalyze the post-translational hydrolysis of arginine residues to form citrulLine. This once obscure modification is now known to play a key role in the etiology of multiple autoimmune diseases (e.g., rheumatoid arthritis, multiple sclerosis, lupus, and ulcerative colitis) and in some forms of cancer. Among the five human PADs (PAD1, -2, -3, -4, and -6), it is unclear which isozyme contributes to disease pathogenesis. Toward the identification of potent, selective, and bioavailable PAD inhibitors that can be used to elucidate the specific roles of each isozyme, we describe tetrazole analogs as suitable backbone amide bond bioisosteres for the parent pan PAD inhibitor Cl-amidine. These tetrazole based analogs are highly potent and show selectivity toward particular isozymes. Importantly, one of the compounds, biphenyl tetrazole tert-butyl Cl-amidine (compound 13), exhibits enhanced Cell killing in a PAD4 expressing osteosarcoma bone marrow (U2OS) Cell Line and can also b...
-
Design, Synthesis, and Biological Evaluation of Tetrazole Analogs of Cl-Amidine as Protein Arginine Deiminase Inhibitors
Journal of medicinal chemistry, 2015Co-Authors: Venkataraman Subramanian, Jason S Knight, Sangram S Parelkar, Lynne J Anguish, Scott A Coonrod, Mariana J Kaplan, Paul R ThompsonAbstract:Protein arginine deiminases (PADs) catalyze the post-translational hydrolysis of arginine residues to form citrulLine. This once obscure modification is now known to play a key role in the etiology of multiple autoimmune diseases (e.g., rheumatoid arthritis, multiple sclerosis, lupus, and ulcerative colitis) and in some forms of cancer. Among the five human PADs (PAD1, -2, -3, -4, and -6), it is unclear which isozyme contributes to disease pathogenesis. Toward the identification of potent, selective, and bioavailable PAD inhibitors that can be used to elucidate the specific roles of each isozyme, we describe tetrazole analogs as suitable backbone amide bond bioisosteres for the parent pan PAD inhibitor Cl-amidine. These tetrazole based analogs are highly potent and show selectivity toward particular isozymes. Importantly, one of the compounds, biphenyl tetrazole tert-butyl Cl-amidine (compound 13), exhibits enhanced Cell killing in a PAD4 expressing osteosarcoma bone marrow (U2OS) Cell Line and can also block the formation of neutrophil extraCellular traps. These bioisosteres represent an important step in our efforts to develop stable, bioavailable, and selective inhibitors for the PADs.
Jee Young Sung - One of the best experts on this subject based on the ideXlab platform.
-
abstract 4996 interferon consensus sequence binding protein icsbp promotes epithelial to mesenchymal transition emt like phenomena Cell motility and invasion via tgf β signaling in U2OS Cells
Cancer Research, 2014Co-Authors: Jee Young Sung, Yong Nyun Kim, H G Kang, J H Yoon, Seogyun Park, June Hyuk Kim, Byungkiu ParkAbstract:Interferon consensus sequence binding protein (ICSBP) is a transcription factor induced by interferon gamma (IFN-γ) and a member of the interferon regulatory factor (IRF) family. ICSBP is predominantly expressed in hematopoietic Cells and regulates the immune response and Cell growth and differentiation. However, little is known about its function in non-hematopoietic Cells. Here we show a novel function for ICSBP in epithelial to mesenchymal transition (EMT)-like phenomena (ELP), Cell motility, and invasion in human osteosarcoma Cell Lines, including U2OS Cells. IFN-γ treatment induced ICSBP expression and EMT-like morphological change in U2OS Cells, which were suppressed by ICSBP knock-down. To further investigate the role of ICSBP in ELP, we established a stable U2OS Cell Line that overexpresses ICSBP. ICSBP expression caused U2OS Cells to have a more elongated shape and an increased vimentin and fibronectin expression. ICSBP expression also promoted adhesiveness, motility, and invasiveness of U2OS Cells. ICSBP up-regulated transforming growth factor (TGF)-β receptors and activated TGF-β signaling cascades, which were responsible for ELP as well as increased Cell motility and invasion. In addition, ICSBP-induced TGF-β receptor activation resulted in the up-regulation of Snail. Knock-down of Snail attenuated the ICSBP-induced augmentation of Cell motility and invasion. Up-regulation of Snail, ELP, and increased invasion by ICSBP expression were also observed in other osteosarcoma Cell Lines, such as Saos-2 and 143B. Furthermore, ICSBP and TGF- β receptor I were expressed in 45/54 (84%) and 47/54 (87%) of human osteosarcoma tissues, respectively, and showed significant correlation (r= 0.47, p= 0.0007) with respect to their expression levels. Taken altogether, these data demonstrate a novel function for ICSBP in ELP, Cell motility, and invasion through the TGF-β and Snail signaling pathways Citation Format: Jee Young Sung, Seog-Yun Park, June Hyuk Kim, Hyun Guy Kang, Jong Hyung Yoon, Yoon Sook Na, Yong-Nyun Kim, Byung-Kiu Park. Interferon consensus sequence binding protein (ICSBP) promotes epithelial to mesenchymal transition (EMT)-like phenomena, Cell motility, and invasion via TGF-β signaling in U2OS Cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4996. doi:10.1158/1538-7445.AM2014-4996
-
interferon consensus sequence binding protein icsbp promotes epithelial to mesenchymal transition emt like phenomena Cell motility and invasion via tgf β signaling in U2OS Cells
Cell Death and Disease, 2014Co-Authors: Jee Young Sung, Yong Nyun Kim, Soyoung Park, Joo Heon Kim, H G Kang, J H Yoon, B K ParkAbstract:Interferon consensus sequence-binding protein (ICSBP) is a transcription factor induced by interferon gamma (IFN-γ) and a member of the interferon regulatory factor (IRF) family. ICSBP is predominantly expressed in hematopoietic Cells and regulates the immune response and Cell growth and differentiation. However, little is known about its function in non-hematopoietic Cells. Here we show a novel function for ICSBP in epithelial-to-mesenchymal transition (EMT)-like phenomena (ELP), Cell motility, and invasion in human osteosarcoma Cell Lines, including U2OS Cells. IFN-γ treatment induced ICSBP expression and EMT-like morphological change in U2OS Cells, which were suppressed by ICSBP knockdown. To further investigate the role of ICSBP in ELP, we established a stable U2OS Cell Line that overexpresses ICSBP. ICSBP expression caused U2OS Cells to have a more elongated shape and an increased vimentin and fibronectin expression. ICSBP expression also promoted adhesiveness, motility, and invasiveness of U2OS Cells. ICSBP upregulated transforming growth factor (TGF)-β receptors and activated TGF-β signaling cascades, which were responsible for ELP as well as increased Cell motility and invasion. In addition, ICSBP-induced TGF-β receptor activation resulted in the upregulation of Snail. Knockdown of Snail attenuated the ICSBP-induced augmentation of Cell motility and invasion. Upregulation of Snail, ELP, and increased invasion by ICSBP expression were also observed in other osteosarcoma Cell Lines, such as Saos-2 and 143B. Furthermore, ICSBP and TGF-β receptor I were expressed in 45/54 (84%) and 47/54 (87%) of human osteosarcoma tissues, respectively, and showed significant correlation (r=0.47, P=0.0007) with respect to their expression levels. Taken altogether, these data demonstrate a novel function for ICSBP in ELP, Cell motility, and invasion through the TGF-β and Snail signaling pathways.
-
abstract 2424 interferon consensus sequence binding protein promotes epithelial to mesenchymal transition and Cell motility in human osteosarcoma Cells
Cancer Research, 2011Co-Authors: Byungkiu Park, Jee Young Sung, Yong Nyun KimAbstract:Interferon consensus sequence binding protein (ICSBP) is a regulatory factor induced by interferon gamma (IFN-γ) and a member of interferon regulatory family (IRF). ICSBP is mainly expressed in hematopoietic Cell and regulates immune response and differentiation but its role in non-hematopoietic Cells is largely unknown. Here we investigated a role of ICSBP in human osteosarcoma U2OS Cell Line. Basal level of ICSBP expression was low but was induced by interferon-γ in U2OS Cells. In addition, induced ICSBP promoted U2OS Cell proliferation. To further elucidate ICSBP functions in osteosarcoma Cells, we generated the U2OS stable Cell Line that overexpresses ICSBP. ICSBP overexpressing Cells grew faster compared with mock Cells and showed morphological changes. ICSBP upregulated TGF-βRI expression resulting in activation of TGF-β signaling pathways. In addition, ICSBP expression altered Cell morphology and increased Cell adhesion and motility. Furthermore ICSBP increased vimentin expression but decreased ZO-1 and E-cadherin expression, which is EMT related phenomena. These motility and EMT related phenomena were inhibited by TGF-βRI inhibitor. Taken together, these findings indicate that ICSBP promotes EMT and Cell motility via TGF-β pathways in U2OS Cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2424. doi:10.1158/1538-7445.AM2011-2424
Khosrow Rezvani - One of the best experts on this subject based on the ideXlab platform.
-
Structural studies of UBXN2A and mortalin interaction and the putative role of silenced UBXN2A in preventing response to chemotherapy
Cell Stress and Chaperones, 2016Co-Authors: Sanam Sane, Ammara Abdullah, Subhash C. Chauhan, Samuel S. Newton, Morgan E. Nelson, Hongmin Wang, Khosrow RezvaniAbstract:Overexpression of the oncoprotein mortalin in cancer Cells and its protein partners enables mortalin to promote multiple oncogenic signaling pathways and effectively antagonize chemotherapy-induced Cell death. A UBX-domain-containing protein, UBXN2A, acts as a potential mortalin inhibitor. This current study determines whether UBXN2A effectively binds to and occupies mortalin’s binding pocket, resulting in a direct improvement in the tumor’s sensitivity to chemotherapy. Molecular modeling of human mortalin’s binding pocket and its binding to the SEP domain of UBXN2A followed by yeast two-hybrid and His-tag pull-down assays revealed that three amino acids (PRO442, ILE558, and LYS555) within the substrate-binding domain of mortalin are crucial for UBXN2A binding to mortalin. As revealed by chase experiments in the presence of cycloheximide, overexpression of UBXN2A seems to interfere with the mortalin-CHIP E3 ubiquitin ligase and consequently suppresses the C‐terminus of the HSC70‐interacting protein (CHIP)-mediated destabilization of p53, resulting in its stabilization in the cytoplasm and upregulation in the nucleus. Overexpression of UBXN2A causes a significant inhibition of Cell proliferation and the migration of colon cancer Cells. We silenced UBXN2A in the human osteosarcoma U2OS Cell Line, an enriched mortalin cancer Cell, followed by a clinical dosage of the chemotherapeutic agent 5-fluorouracil (5-FU). The UBXN2A knockout U2OS Cells revealed that UBXNA is essential for the cytotoxic effect achieved by 5-FU. UBXN2A overexpression markedly increased the apoptotic response of U2OS Cells to the 5-FU. In addition, silencing of UBXN2A protein suppresses apoptosis enhanced by UBXN2A overexpression in U2OS. The knowledge gained from this study provides insights into the mechanistic role of UBXN2A as a potent mortalin inhibitor and as a potential chemotherapy sensitizer for clinical application.
Yong Nyun Kim - One of the best experts on this subject based on the ideXlab platform.
-
abstract 4996 interferon consensus sequence binding protein icsbp promotes epithelial to mesenchymal transition emt like phenomena Cell motility and invasion via tgf β signaling in U2OS Cells
Cancer Research, 2014Co-Authors: Jee Young Sung, Yong Nyun Kim, H G Kang, J H Yoon, Seogyun Park, June Hyuk Kim, Byungkiu ParkAbstract:Interferon consensus sequence binding protein (ICSBP) is a transcription factor induced by interferon gamma (IFN-γ) and a member of the interferon regulatory factor (IRF) family. ICSBP is predominantly expressed in hematopoietic Cells and regulates the immune response and Cell growth and differentiation. However, little is known about its function in non-hematopoietic Cells. Here we show a novel function for ICSBP in epithelial to mesenchymal transition (EMT)-like phenomena (ELP), Cell motility, and invasion in human osteosarcoma Cell Lines, including U2OS Cells. IFN-γ treatment induced ICSBP expression and EMT-like morphological change in U2OS Cells, which were suppressed by ICSBP knock-down. To further investigate the role of ICSBP in ELP, we established a stable U2OS Cell Line that overexpresses ICSBP. ICSBP expression caused U2OS Cells to have a more elongated shape and an increased vimentin and fibronectin expression. ICSBP expression also promoted adhesiveness, motility, and invasiveness of U2OS Cells. ICSBP up-regulated transforming growth factor (TGF)-β receptors and activated TGF-β signaling cascades, which were responsible for ELP as well as increased Cell motility and invasion. In addition, ICSBP-induced TGF-β receptor activation resulted in the up-regulation of Snail. Knock-down of Snail attenuated the ICSBP-induced augmentation of Cell motility and invasion. Up-regulation of Snail, ELP, and increased invasion by ICSBP expression were also observed in other osteosarcoma Cell Lines, such as Saos-2 and 143B. Furthermore, ICSBP and TGF- β receptor I were expressed in 45/54 (84%) and 47/54 (87%) of human osteosarcoma tissues, respectively, and showed significant correlation (r= 0.47, p= 0.0007) with respect to their expression levels. Taken altogether, these data demonstrate a novel function for ICSBP in ELP, Cell motility, and invasion through the TGF-β and Snail signaling pathways Citation Format: Jee Young Sung, Seog-Yun Park, June Hyuk Kim, Hyun Guy Kang, Jong Hyung Yoon, Yoon Sook Na, Yong-Nyun Kim, Byung-Kiu Park. Interferon consensus sequence binding protein (ICSBP) promotes epithelial to mesenchymal transition (EMT)-like phenomena, Cell motility, and invasion via TGF-β signaling in U2OS Cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4996. doi:10.1158/1538-7445.AM2014-4996
-
interferon consensus sequence binding protein icsbp promotes epithelial to mesenchymal transition emt like phenomena Cell motility and invasion via tgf β signaling in U2OS Cells
Cell Death and Disease, 2014Co-Authors: Jee Young Sung, Yong Nyun Kim, Soyoung Park, Joo Heon Kim, H G Kang, J H Yoon, B K ParkAbstract:Interferon consensus sequence-binding protein (ICSBP) is a transcription factor induced by interferon gamma (IFN-γ) and a member of the interferon regulatory factor (IRF) family. ICSBP is predominantly expressed in hematopoietic Cells and regulates the immune response and Cell growth and differentiation. However, little is known about its function in non-hematopoietic Cells. Here we show a novel function for ICSBP in epithelial-to-mesenchymal transition (EMT)-like phenomena (ELP), Cell motility, and invasion in human osteosarcoma Cell Lines, including U2OS Cells. IFN-γ treatment induced ICSBP expression and EMT-like morphological change in U2OS Cells, which were suppressed by ICSBP knockdown. To further investigate the role of ICSBP in ELP, we established a stable U2OS Cell Line that overexpresses ICSBP. ICSBP expression caused U2OS Cells to have a more elongated shape and an increased vimentin and fibronectin expression. ICSBP expression also promoted adhesiveness, motility, and invasiveness of U2OS Cells. ICSBP upregulated transforming growth factor (TGF)-β receptors and activated TGF-β signaling cascades, which were responsible for ELP as well as increased Cell motility and invasion. In addition, ICSBP-induced TGF-β receptor activation resulted in the upregulation of Snail. Knockdown of Snail attenuated the ICSBP-induced augmentation of Cell motility and invasion. Upregulation of Snail, ELP, and increased invasion by ICSBP expression were also observed in other osteosarcoma Cell Lines, such as Saos-2 and 143B. Furthermore, ICSBP and TGF-β receptor I were expressed in 45/54 (84%) and 47/54 (87%) of human osteosarcoma tissues, respectively, and showed significant correlation (r=0.47, P=0.0007) with respect to their expression levels. Taken altogether, these data demonstrate a novel function for ICSBP in ELP, Cell motility, and invasion through the TGF-β and Snail signaling pathways.
-
abstract 2424 interferon consensus sequence binding protein promotes epithelial to mesenchymal transition and Cell motility in human osteosarcoma Cells
Cancer Research, 2011Co-Authors: Byungkiu Park, Jee Young Sung, Yong Nyun KimAbstract:Interferon consensus sequence binding protein (ICSBP) is a regulatory factor induced by interferon gamma (IFN-γ) and a member of interferon regulatory family (IRF). ICSBP is mainly expressed in hematopoietic Cell and regulates immune response and differentiation but its role in non-hematopoietic Cells is largely unknown. Here we investigated a role of ICSBP in human osteosarcoma U2OS Cell Line. Basal level of ICSBP expression was low but was induced by interferon-γ in U2OS Cells. In addition, induced ICSBP promoted U2OS Cell proliferation. To further elucidate ICSBP functions in osteosarcoma Cells, we generated the U2OS stable Cell Line that overexpresses ICSBP. ICSBP overexpressing Cells grew faster compared with mock Cells and showed morphological changes. ICSBP upregulated TGF-βRI expression resulting in activation of TGF-β signaling pathways. In addition, ICSBP expression altered Cell morphology and increased Cell adhesion and motility. Furthermore ICSBP increased vimentin expression but decreased ZO-1 and E-cadherin expression, which is EMT related phenomena. These motility and EMT related phenomena were inhibited by TGF-βRI inhibitor. Taken together, these findings indicate that ICSBP promotes EMT and Cell motility via TGF-β pathways in U2OS Cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2424. doi:10.1158/1538-7445.AM2011-2424
