The Experts below are selected from a list of 11520 Experts worldwide ranked by ideXlab platform
Jian Wang - One of the best experts on this subject based on the ideXlab platform.
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RNA Splicing Factor USP39 promotes glioma progression by inducing TAZ mRNA maturation.
Oncogene, 2019Co-Authors: Kaikai Ding, Xin Zhang, Bin Huang, Anjing Chen, Di Zhang, Xinyu Wang, Jian WangAbstract:Increasing evidence demonstrates that ubiquitin specific protease 39 (USP39) plays an oncogenic role in various human tumors. Here, using expression analysis of the publicly available Oncomine database, clinical glioma patient samples, and glioma cells, we found that USP39 was overexpressed in human gliomas. Knockdown of USP39 in glioma cells demonstrated that the protein promoted cell growth, invasion and migration in vitro and in a tumor model in nude mice. To identify mediators of USP39 growth-promoting properties, we used luciferase reporter constructs under transcriptional control of various promoters specific to seven canonical cancer-associated pathways. Luciferase activity from a synthetic TEAD-dependent YAP/TAZ-responsive reporter, as a direct readout of the Hippo signaling pathway, was decreased by 92% in cells with USP39 knockdown, whereas the luciferase activities from the other six cancer pathways, including MAPK/ERK, MAPK/JNK, NFκB, Notch, TGFβ, and Wnt, remained unchanged. TAZ protein expression however was decreased independent of canonical Hippo signaling. Immunohistochemistry revealed a positive correlation between USP39 and TAZ proteins in orthotopic xenografts derived from modified glioma cells expressing USP39 shRNAs and primary human glioma samples (p
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RNA Splicing Factor usp39 promotes glioma progression by inducing taz mRNA maturation
Oncogene, 2019Co-Authors: Kaikai Ding, Xin Zhang, Bin Huang, Anjing Chen, Di Zhang, Xinyu Wang, Jian WangAbstract:Increasing evidence demonstrates that ubiquitin specific protease 39 (USP39) plays an oncogenic role in various human tumors. Here, using expression analysis of the publicly available Oncomine database, clinical glioma patient samples, and glioma cells, we found that USP39 was overexpressed in human gliomas. Knockdown of USP39 in glioma cells demonstrated that the protein promoted cell growth, invasion and migration in vitro and in a tumor model in nude mice. To identify mediators of USP39 growth-promoting properties, we used luciferase reporter constructs under transcriptional control of various promoters specific to seven canonical cancer-associated pathways. Luciferase activity from a synthetic TEAD-dependent YAP/TAZ-responsive reporter, as a direct readout of the Hippo signaling pathway, was decreased by 92% in cells with USP39 knockdown, whereas the luciferase activities from the other six cancer pathways, including MAPK/ERK, MAPK/JNK, NFκB, Notch, TGFβ, and Wnt, remained unchanged. TAZ protein expression however was decreased independent of canonical Hippo signaling. Immunohistochemistry revealed a positive correlation between USP39 and TAZ proteins in orthotopic xenografts derived from modified glioma cells expressing USP39 shRNAs and primary human glioma samples (p < 0.05). Finally, loss of USP39 decreased TAZ pre-mRNA Splicing efficiency in glioma cells in vitro, which led to reduced levels of TAZ protein. In summary, USP39 has oncogenic properties that increase TAZ protein levels by inducing maturation of its mRNA. USP39 therefore provides a novel therapeutic target for the treatment of human glioma.
Stephen H Howell - One of the best experts on this subject based on the ideXlab platform.
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Endoplasmic Reticulum (ER) Stress Response and Its Physiological Roles in Plants
International journal of molecular sciences, 2013Co-Authors: Yan Deng, Renu Srivastava, Stephen H HowellAbstract:The endoplasmic reticulum (ER) stress response is a highly conserved mechanism that results from the accumulation of unfolded or misfolded proteins in the ER. The response plays an important role in allowing plants to sense and respond to adverse environmental conditions, such as heat stress, salt stress and pathogen infection. Since the ER is a well-controlled microenvironment for proper protein synthesis and folding, it is highly susceptible to stress conditions. Accumulation of unfolded or misfolded proteins activates a signaling pathway, called the unfolded protein response (UPR), which acts to relieve ER stress and, if unsuccessful, leads to cell death. Plants have two arms of the UPR signaling pathway, an arm involving the proteolytic processing of membrane-associated basic leucine zipper domain (bZIP) transcription Factors and an arm involving RNA Splicing Factor, IRE1, and its mRNA target. These signaling pathways play an important role in determining the cell's fate in response to stress conditions.
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Endoplasmic Reticulum Stress Responses in Plants
Annual review of plant biology, 2013Co-Authors: Stephen H HowellAbstract:Endoplasmic reticulum (ER) stress is of considerable interest to plant biologists because it occurs in plants subjected to adverse environmental conditions. ER stress responses mitigate the damage caused by stress and confer levels of stress tolerance to plants. ER stress is activated by misfolded proteins that accumulate in the ER under adverse environmental conditions. Under these conditions, the demand for protein folding exceeds the capacity of the system, which sets off the unfolded protein response (UPR). Two arms of the UPR signaling pathway have been described in plants: one that involves two ER membrane-associated transcription Factors (bZIP17 and bZIP28) and another that involves a dual protein kinase (RNA-Splicing Factor IRE1) and its target RNA (bZIP60). Under mild or short-term stress conditions, signaling from IRE1 activates autophagy, a cell survival response. But under severe or chronic stress conditions, ER stress can lead to cell death.
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heat induces the Splicing by ire1 of a mRNA encoding a transcription Factor involved in the unfolded protein response in arabidopsis
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Yan Deng, Sabrina Humbert, Renu Srivastava, Steven J Rothstein, Stephen H HowellAbstract:Adverse environmental conditions produce endoplasmic reticulum (ER) stress in plants. In response to heat or ER stress agents, Arabidopsis seedlings mitigate stress damage by activating ER-associated transcription Factors and a RNA Splicing Factor, IRE1b. IRE1b splices the mRNA-encoding bZIP60, a basic leucine-zipper domain containing transcription Factor associated with the unfolded protein response in plants. bZIP60 is required for the up-regulation of BINDING PROTEIN3 (BIP3) in response to ER stress, and loss-of-function mutations in IRE1b or point mutations in the Splicing site of bZIP60 mRNA are defective in BIP3 induction. These findings demonstrate that bZIP60 in plants is activated by RNA Splicing and afford opportunities for monitoring and modulating stress responses in plants.
Richard A. Baines - One of the best experts on this subject based on the ideXlab platform.
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Regulation of membrane excitability: a convergence on voltage-gated sodium conductance
Molecular Neurobiology, 2015Co-Authors: Richard A. BainesAbstract:The voltage-gated sodium channel (Na_v) plays a key role in regulation of neuronal excitability. Aberrant regulation of Na_v expression and/or function can result in an imbalance in neuronal activity which can progress to epilepsy. Regulation of Na_v activity is achieved by coordination of a multitude of mechanisms including RNA alteRNAtive Splicing and translational repression. Understanding of these regulatory mechanisms is complicated by extensive genetic redundancy: the mammalian genome encodes ten Na_vs. By contrast, the genome of the fruitfly, Drosophila melanogaster , contains just one Na_v homologue, encoded by paralytic ( DmNa _ v ). Analysis of Splicing in DmNa _ v shows variants exhibit distinct gating properties including varying magnitudes of persistent sodium current (I_NaP). Splicing by Pasilla, an identified RNA Splicing Factor, alters I_NaP magnitude as part of an activity-dependent mechanism. Enhanced I_NaP promotes membrane hyperexcitability that is associated with seizure-like behaviour in Drosophila . Nova-2, a mammalian Pasilla homologue, has also been linked to Splicing of Na_vs and, moreover, mouse gene knockouts display seizure-like behaviour. Expression level of Na_vs is also regulated through a mechanism of translational repression in both flies and mammals. The translational repressor Pumilio (Pum) can bind to Na _ v transcripts and repress the normal process of translation, thus regulating sodium current (I_Na) density in neurons. Pum2-deficient mice exhibit spontaneous EEG abnormalities. Taken together, aberrant regulation of Na_v function and/or expression is often epileptogenic. As such, a better understanding of regulation of membrane excitability through RNA alteRNAtive Splicing and translational repression of Na_vs should provide new leads to treat epilepsy.
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regulation of membrane excitability a convergence on voltage gated sodium conductance
Molecular Neurobiology, 2015Co-Authors: Richard A. BainesAbstract:The voltage-gated sodium channel (Nav) plays a key role in regulation of neuronal excitability. Aberrant regulation of Nav expression and/or function can result in an imbalance in neuronal activity which can progress to epilepsy. Regulation of Nav activity is achieved by coordination of a multitude of mechanisms including RNA alteRNAtive Splicing and translational repression. Understanding of these regulatory mechanisms is complicated by extensive genetic redundancy: the mammalian genome encodes ten Navs. By contrast, the genome of the fruitfly, Drosophila melanogaster, contains just one Nav homologue, encoded by paralytic (DmNav). Analysis of Splicing in DmNav shows variants exhibit distinct gating properties including varying magnitudes of persistent sodium current (INaP). Splicing by Pasilla, an identified RNA Splicing Factor, alters INaP magnitude as part of an activity-dependent mechanism. Enhanced INaP promotes membrane hyperexcitability that is associated with seizure-like behaviour in Drosophila. Nova-2, a mammalian Pasilla homologue, has also been linked to Splicing of Navs and, moreover, mouse gene knockouts display seizure-like behaviour.
Kaikai Ding - One of the best experts on this subject based on the ideXlab platform.
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RNA Splicing Factor USP39 promotes glioma progression by inducing TAZ mRNA maturation.
Oncogene, 2019Co-Authors: Kaikai Ding, Xin Zhang, Bin Huang, Anjing Chen, Di Zhang, Xinyu Wang, Jian WangAbstract:Increasing evidence demonstrates that ubiquitin specific protease 39 (USP39) plays an oncogenic role in various human tumors. Here, using expression analysis of the publicly available Oncomine database, clinical glioma patient samples, and glioma cells, we found that USP39 was overexpressed in human gliomas. Knockdown of USP39 in glioma cells demonstrated that the protein promoted cell growth, invasion and migration in vitro and in a tumor model in nude mice. To identify mediators of USP39 growth-promoting properties, we used luciferase reporter constructs under transcriptional control of various promoters specific to seven canonical cancer-associated pathways. Luciferase activity from a synthetic TEAD-dependent YAP/TAZ-responsive reporter, as a direct readout of the Hippo signaling pathway, was decreased by 92% in cells with USP39 knockdown, whereas the luciferase activities from the other six cancer pathways, including MAPK/ERK, MAPK/JNK, NFκB, Notch, TGFβ, and Wnt, remained unchanged. TAZ protein expression however was decreased independent of canonical Hippo signaling. Immunohistochemistry revealed a positive correlation between USP39 and TAZ proteins in orthotopic xenografts derived from modified glioma cells expressing USP39 shRNAs and primary human glioma samples (p
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RNA Splicing Factor usp39 promotes glioma progression by inducing taz mRNA maturation
Oncogene, 2019Co-Authors: Kaikai Ding, Xin Zhang, Bin Huang, Anjing Chen, Di Zhang, Xinyu Wang, Jian WangAbstract:Increasing evidence demonstrates that ubiquitin specific protease 39 (USP39) plays an oncogenic role in various human tumors. Here, using expression analysis of the publicly available Oncomine database, clinical glioma patient samples, and glioma cells, we found that USP39 was overexpressed in human gliomas. Knockdown of USP39 in glioma cells demonstrated that the protein promoted cell growth, invasion and migration in vitro and in a tumor model in nude mice. To identify mediators of USP39 growth-promoting properties, we used luciferase reporter constructs under transcriptional control of various promoters specific to seven canonical cancer-associated pathways. Luciferase activity from a synthetic TEAD-dependent YAP/TAZ-responsive reporter, as a direct readout of the Hippo signaling pathway, was decreased by 92% in cells with USP39 knockdown, whereas the luciferase activities from the other six cancer pathways, including MAPK/ERK, MAPK/JNK, NFκB, Notch, TGFβ, and Wnt, remained unchanged. TAZ protein expression however was decreased independent of canonical Hippo signaling. Immunohistochemistry revealed a positive correlation between USP39 and TAZ proteins in orthotopic xenografts derived from modified glioma cells expressing USP39 shRNAs and primary human glioma samples (p < 0.05). Finally, loss of USP39 decreased TAZ pre-mRNA Splicing efficiency in glioma cells in vitro, which led to reduced levels of TAZ protein. In summary, USP39 has oncogenic properties that increase TAZ protein levels by inducing maturation of its mRNA. USP39 therefore provides a novel therapeutic target for the treatment of human glioma.
Chikao Yutani - One of the best experts on this subject based on the ideXlab platform.
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expression of a novel RNA Splicing Factor ra301 tra2β in vascular lesions and its role in smooth muscle cell proliferation
American Journal of Pathology, 2001Co-Authors: Yoshitane Tsukamoto, Noriyuki Matsuo, Kentaro Ozawa, Osamu Hori, Toshio Higashi, Junya Nishizaki, Norimitsu Tohnai, Izumi Nagata, Kiyoshi Kawano, Chikao YutaniAbstract:RA301/Tra2β, a sequence-specific RNA-binding protein, was first cloned as a stress molecule in re-oxygenated astrocytes. In human vascular tissues, we have found enhanced RA301/Tra2β expression in coronary artery with intimal thickening, and atherosclerotic aorta. Balloon injury to the rat carotid artery induced RA301/Tra2β transcripts followed by expression of the antigen, which was detected in medial and neointimal vascular smooth muscle cells (VSMCs). In cultured VSMCs, hypoxia/re-oxygenation caused induction of RA301/Tra2β and was accompanied by cell proliferation, both of which were blocked by the addition of either diphenyl iodonium, a NADPH oxidase inhibitor, PD98059, a mitogen-activated protein kinase kinase inhibitor, or antisense oligonucleotide for RA301/Tra2β. Consistent with a link between RA301/Tra2β and cell proliferation, platelet-derived growth Factor also induced expression of RA301/Tra2β in cultured VSMCs. These data suggest a possible role for RA301/Tra2β in the regulation of VSMC proliferation, especially in the setting of hypoxia/re-oxygenation-induced cell stress.
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Expression of a Novel RNA-Splicing Factor, RA301/Tra2β, in Vascular Lesions and Its Role in Smooth Muscle Cell Proliferation
The American journal of pathology, 2001Co-Authors: Yoshitane Tsukamoto, Noriyuki Matsuo, Kentaro Ozawa, Osamu Hori, Toshio Higashi, Junya Nishizaki, Norimitsu Tohnai, Izumi Nagata, Kiyoshi Kawano, Chikao YutaniAbstract:RA301/Tra2β, a sequence-specific RNA-binding protein, was first cloned as a stress molecule in re-oxygenated astrocytes. In human vascular tissues, we have found enhanced RA301/Tra2β expression in coronary artery with intimal thickening, and atherosclerotic aorta. Balloon injury to the rat carotid artery induced RA301/Tra2β transcripts followed by expression of the antigen, which was detected in medial and neointimal vascular smooth muscle cells (VSMCs). In cultured VSMCs, hypoxia/re-oxygenation caused induction of RA301/Tra2β and was accompanied by cell proliferation, both of which were blocked by the addition of either diphenyl iodonium, a NADPH oxidase inhibitor, PD98059, a mitogen-activated protein kinase kinase inhibitor, or antisense oligonucleotide for RA301/Tra2β. Consistent with a link between RA301/Tra2β and cell proliferation, platelet-derived growth Factor also induced expression of RA301/Tra2β in cultured VSMCs. These data suggest a possible role for RA301/Tra2β in the regulation of VSMC proliferation, especially in the setting of hypoxia/re-oxygenation-induced cell stress.
