The Experts below are selected from a list of 23946 Experts worldwide ranked by ideXlab platform
Nico P. Dantuma - One of the best experts on this subject based on the ideXlab platform.
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Illuminating the ubiquitin/Proteasome System
Experimental cell research, 2010Co-Authors: Florian A. Salomons, Klára Ács, Nico P. DantumaAbstract:The ubiquitin/Proteasome System (UPS) is responsible for the regulated processive degradation of proteins residing in the cytosol, nucleus, and endoplasmic reticulum. The two central players are ubiquitin, a small protein that is conjugated to substrates, and the Proteasome, a large multi-subunit proteolytic complex that executes degradation of ubiquitylated proteins. Ubiquitylation and proteasomal degradation are highly dynamic processes. During the last decade, many researchers have started taking advantage of fluorescent proteins, which allow studying the dynamic nature of this System in the context of its natural environment: the living cell. In this review, we will summarize studies that have implemented this approach to examine the UPS and discuss novel insights in the dynamic organization of the UPS.
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Stressing the ubiquitin-Proteasome System
Cardiovascular research, 2009Co-Authors: Nico P. Dantuma, Kristina LindstenAbstract:Unfolded and misfolded proteins are inherently toxic to cells and have to be quickly and efficiently eliminated before they intoxicate the intracellular environment. This is of particular importance during proteotoxic stress when, as a consequence of intrinsic or extrinsic factors, the levels of misfolded proteins are transiently or persistently elevated. To meet this demand, metazoan cells have developed specific protein quality control mechanisms that allow the identification and proper handling of non-native proteins. An important defence mechanism is the specific destruction of these proteins by the ubiquitin-Proteasome System (UPS). A number of studies have shown that various proteotoxic stress conditions can cause functional impairment of the UPS resulting in cellular dysfunction and apoptosis. In this review, we will summarize our current understanding of proteotoxic stress-induced dysfunction of the UPS and some of its implications for human pathologies.
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A transgenic mouse model of the ubiquitin/Proteasome System.
Nature biotechnology, 2003Co-Authors: Kristina Lindsten, Maria G Masucci, Victoria Menendez-benito, Nico P. DantumaAbstract:Impairment of the ubiquitin/Proteasome System has been proposed to play a role in neurodegenerative disorders such as Alzheimer and Parkinson diseases. Although recent studies confirmed that some disease-related proteins block proteasomal degradation, and despite the existence of excellent animal models of both diseases, in vivo data about the System are lacking. We have developed a model for in vivo analysis of the ubiquitin/Proteasome System by generating mouse strains transgenic for a green fluorescent protein (GFP) reporter carrying a constitutively active degradation signal. Administration of Proteasome inhibitors to the transgenic animals resulted in a substantial accumulation of GFP in multiple tissues, confirming the in vivo functionality of the reporter. Moreover, accumulation of the reporter was induced in primary neurons by UBB+1, an aberrant ubiquitin found in Alzheimer disease. These transgenic animals provide a tool for monitoring the status of the ubiquitin/Proteasome System in physiologic or pathologic conditions.
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a transgenic mouse model of the ubiquitin Proteasome System
Nature Biotechnology, 2003Co-Authors: Kristina Lindsten, Victoria Menendezbenito, Maria G Masucci, Nico P. DantumaAbstract:Impairment of the ubiquitin/Proteasome System has been proposed to play a role in neurodegenerative disorders such as Alzheimer and Parkinson diseases. Although recent studies confirmed that some disease-related proteins block proteasomal degradation, and despite the existence of excellent animal models of both diseases, in vivo data about the System are lacking. We have developed a model for in vivo analysis of the ubiquitin/Proteasome System by generating mouse strains transgenic for a green fluorescent protein (GFP) reporter carrying a constitutively active degradation signal. Administration of Proteasome inhibitors to the transgenic animals resulted in a substantial accumulation of GFP in multiple tissues, confirming the in vivo functionality of the reporter. Moreover, accumulation of the reporter was induced in primary neurons by UBB+1, an aberrant ubiquitin found in Alzheimer disease. These transgenic animals provide a tool for monitoring the status of the ubiquitin/Proteasome System in physiologic or pathologic conditions.
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Monitoring the ubiquitin/Proteasome System in conformational diseases
Ageing research reviews, 2003Co-Authors: Kristina Lindsten, Nico P. DantumaAbstract:Controlled proteolysis of regulatory or aberrant proteins by the ubiquitin/Proteasome System is indispensable for cell viability. Conformational diseases such as Alzheimer's, Parkinson's and Huntington's disease are characterised by the accumulation of misfolded or aggregation-prone proteins. Since these proteins are typical substrates of the ubiquitin/Proteasome System, it is not surprising that various models propose impairment of this System as a contributing factor to the pathology of conformational disorders. The complex nature of the ubiquitin/Proteasome System and its universal role in cell physiology however turns evaluation of these attractive hypotheses into a major challenge. Several reporter substrates for the ubiquitin/Proteasome System have recently been developed to facilitate functional studies of the System in living cells. In this review, we will discuss these new tools as well as the proteins associated with conformational disease that have been studied with these reporters.
Stua Nelis - One of the best experts on this subject based on the ideXlab platform.
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the ubiquitin Proteasome System central modifier of plant signalling
New Phytologist, 2012Co-Authors: Ari Sadanandom, Mark Ailey, Richard Ewa, Jack Lee, Stua NelisAbstract:Contents Summary 13 I. Brief history 13 II. Components of the ubiquitin–Proteasome System 14 III. Ubiquitin-mediated degradation: a recurrent theme in the plant life cycle 18 IV. Conclusion and future prospects 25 Acknowledgements 25 References 25 Summary Ubiquitin is well established as a major modifier of signalling in eukaryotes. However, the extent to which plants rely on ubiquitin for regulating their lifecycle is only recently becoming apparent. This is underlined by the over-representation of genes encoding ubiquitin-metabolizing enzymes in Arabidopsis when compared with other model eukaryotes. The main characteristic of ubiquitination is the conjugation of ubiquitin onto lysine residues of acceptor proteins. In most cases the targeted protein is rapidly degraded by the 26S Proteasome, the major proteolysis machinery in eukaryotic cells. The ubiquitin–Proteasome System is responsible for removing most abnormal peptides and short-lived cellular regulators, which, in turn, control many processes. This allows cells to respond rapidly to intracellular signals and changing environmental conditions. This review maps out the roles of the components of the ubiquitin–Proteasome System with emphasis on areas where future research is urgently needed. We provide a flavour of the diverse aspects of plant lifecycle where the ubiquitin–Proteasome System is implicated. We aim to highlight common themes using key examples that reiterate the importance of the ubiquitin–Proteasome System to plants. The future challenge in plant biology is to define the targets for ubiquitination, their interactors and their molecular function within the regulatory context.
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The ubiquitin–Proteasome System: central modifier of plant signalling
The New phytologist, 2012Co-Authors: Ari Sadanandom, Jack Lee, Mark Bailey, Richard Ewan, Stua NelisAbstract:Contents Summary 13 I. Brief history 13 II. Components of the ubiquitin–Proteasome System 14 III. Ubiquitin-mediated degradation: a recurrent theme in the plant life cycle 18 IV. Conclusion and future prospects 25 Acknowledgements 25 References 25 Summary Ubiquitin is well established as a major modifier of signalling in eukaryotes. However, the extent to which plants rely on ubiquitin for regulating their lifecycle is only recently becoming apparent. This is underlined by the over-representation of genes encoding ubiquitin-metabolizing enzymes in Arabidopsis when compared with other model eukaryotes. The main characteristic of ubiquitination is the conjugation of ubiquitin onto lysine residues of acceptor proteins. In most cases the targeted protein is rapidly degraded by the 26S Proteasome, the major proteolysis machinery in eukaryotic cells. The ubiquitin–Proteasome System is responsible for removing most abnormal peptides and short-lived cellular regulators, which, in turn, control many processes. This allows cells to respond rapidly to intracellular signals and changing environmental conditions. This review maps out the roles of the components of the ubiquitin–Proteasome System with emphasis on areas where future research is urgently needed. We provide a flavour of the diverse aspects of plant lifecycle where the ubiquitin–Proteasome System is implicated. We aim to highlight common themes using key examples that reiterate the importance of the ubiquitin–Proteasome System to plants. The future challenge in plant biology is to define the targets for ubiquitination, their interactors and their molecular function within the regulatory context.
Kristina Lindsten - One of the best experts on this subject based on the ideXlab platform.
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Stressing the ubiquitin-Proteasome System
Cardiovascular research, 2009Co-Authors: Nico P. Dantuma, Kristina LindstenAbstract:Unfolded and misfolded proteins are inherently toxic to cells and have to be quickly and efficiently eliminated before they intoxicate the intracellular environment. This is of particular importance during proteotoxic stress when, as a consequence of intrinsic or extrinsic factors, the levels of misfolded proteins are transiently or persistently elevated. To meet this demand, metazoan cells have developed specific protein quality control mechanisms that allow the identification and proper handling of non-native proteins. An important defence mechanism is the specific destruction of these proteins by the ubiquitin-Proteasome System (UPS). A number of studies have shown that various proteotoxic stress conditions can cause functional impairment of the UPS resulting in cellular dysfunction and apoptosis. In this review, we will summarize our current understanding of proteotoxic stress-induced dysfunction of the UPS and some of its implications for human pathologies.
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A transgenic mouse model of the ubiquitin/Proteasome System.
Nature biotechnology, 2003Co-Authors: Kristina Lindsten, Maria G Masucci, Victoria Menendez-benito, Nico P. DantumaAbstract:Impairment of the ubiquitin/Proteasome System has been proposed to play a role in neurodegenerative disorders such as Alzheimer and Parkinson diseases. Although recent studies confirmed that some disease-related proteins block proteasomal degradation, and despite the existence of excellent animal models of both diseases, in vivo data about the System are lacking. We have developed a model for in vivo analysis of the ubiquitin/Proteasome System by generating mouse strains transgenic for a green fluorescent protein (GFP) reporter carrying a constitutively active degradation signal. Administration of Proteasome inhibitors to the transgenic animals resulted in a substantial accumulation of GFP in multiple tissues, confirming the in vivo functionality of the reporter. Moreover, accumulation of the reporter was induced in primary neurons by UBB+1, an aberrant ubiquitin found in Alzheimer disease. These transgenic animals provide a tool for monitoring the status of the ubiquitin/Proteasome System in physiologic or pathologic conditions.
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a transgenic mouse model of the ubiquitin Proteasome System
Nature Biotechnology, 2003Co-Authors: Kristina Lindsten, Victoria Menendezbenito, Maria G Masucci, Nico P. DantumaAbstract:Impairment of the ubiquitin/Proteasome System has been proposed to play a role in neurodegenerative disorders such as Alzheimer and Parkinson diseases. Although recent studies confirmed that some disease-related proteins block proteasomal degradation, and despite the existence of excellent animal models of both diseases, in vivo data about the System are lacking. We have developed a model for in vivo analysis of the ubiquitin/Proteasome System by generating mouse strains transgenic for a green fluorescent protein (GFP) reporter carrying a constitutively active degradation signal. Administration of Proteasome inhibitors to the transgenic animals resulted in a substantial accumulation of GFP in multiple tissues, confirming the in vivo functionality of the reporter. Moreover, accumulation of the reporter was induced in primary neurons by UBB+1, an aberrant ubiquitin found in Alzheimer disease. These transgenic animals provide a tool for monitoring the status of the ubiquitin/Proteasome System in physiologic or pathologic conditions.
-
Monitoring the ubiquitin/Proteasome System in conformational diseases
Ageing research reviews, 2003Co-Authors: Kristina Lindsten, Nico P. DantumaAbstract:Controlled proteolysis of regulatory or aberrant proteins by the ubiquitin/Proteasome System is indispensable for cell viability. Conformational diseases such as Alzheimer's, Parkinson's and Huntington's disease are characterised by the accumulation of misfolded or aggregation-prone proteins. Since these proteins are typical substrates of the ubiquitin/Proteasome System, it is not surprising that various models propose impairment of this System as a contributing factor to the pathology of conformational disorders. The complex nature of the ubiquitin/Proteasome System and its universal role in cell physiology however turns evaluation of these attractive hypotheses into a major challenge. Several reporter substrates for the ubiquitin/Proteasome System have recently been developed to facilitate functional studies of the System in living cells. In this review, we will discuss these new tools as well as the proteins associated with conformational disease that have been studied with these reporters.
Alan L. Schwartz - One of the best experts on this subject based on the ideXlab platform.
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E2A protein degradation by the ubiquitin-Proteasome System is stage-dependent during muscle differentiation
Oncogene, 2006Co-Authors: Liping Sun, Julie S. Trausch-azar, Aaron Ciechanover, Alan L. SchwartzAbstract:E2A protein degradation by the ubiquitin-Proteasome System is stage-dependent during muscle differentiation
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The nuclear ubiquitin-Proteasome System degrades MyoD.
The Journal of biological chemistry, 2001Co-Authors: Z. Elizabeth Floyd, Julie S. Trausch-azar, Eyal Reinstein, Aaron Ciechanover, Alan L. SchwartzAbstract:Many short-lived nuclear proteins are targeted for degradation by the ubiquitin-Proteasome pathway. The role of the nucleus in regulating the turnover of these proteins is not well defined, although many components of the ubiquitin-Proteasome System are localized in the nucleus. We have used nucleoplasm from highly purified HeLa nuclei to examine the degradation of a physiological substrate of the ubiquitin-Proteasome System (MyoD). In vitro studies using inhibitors of the System demonstrate MyoD is degraded via the ubiquitin-Proteasome pathway in HeLa nucleoplasm. Purified nucleoplasm in vitro also supports the generation of high molecular mass MyoD-ubiquitin adducts. In addition, in vivo studies, using leptomycin B to inhibit nuclear export, demonstrate that MyoD is degraded in HeLa cells by the nuclear ubiquitin-Proteasome System.
Ari Sadanandom - One of the best experts on this subject based on the ideXlab platform.
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the ubiquitin Proteasome System central modifier of plant signalling
New Phytologist, 2012Co-Authors: Ari Sadanandom, Mark Ailey, Richard Ewa, Jack Lee, Stua NelisAbstract:Contents Summary 13 I. Brief history 13 II. Components of the ubiquitin–Proteasome System 14 III. Ubiquitin-mediated degradation: a recurrent theme in the plant life cycle 18 IV. Conclusion and future prospects 25 Acknowledgements 25 References 25 Summary Ubiquitin is well established as a major modifier of signalling in eukaryotes. However, the extent to which plants rely on ubiquitin for regulating their lifecycle is only recently becoming apparent. This is underlined by the over-representation of genes encoding ubiquitin-metabolizing enzymes in Arabidopsis when compared with other model eukaryotes. The main characteristic of ubiquitination is the conjugation of ubiquitin onto lysine residues of acceptor proteins. In most cases the targeted protein is rapidly degraded by the 26S Proteasome, the major proteolysis machinery in eukaryotic cells. The ubiquitin–Proteasome System is responsible for removing most abnormal peptides and short-lived cellular regulators, which, in turn, control many processes. This allows cells to respond rapidly to intracellular signals and changing environmental conditions. This review maps out the roles of the components of the ubiquitin–Proteasome System with emphasis on areas where future research is urgently needed. We provide a flavour of the diverse aspects of plant lifecycle where the ubiquitin–Proteasome System is implicated. We aim to highlight common themes using key examples that reiterate the importance of the ubiquitin–Proteasome System to plants. The future challenge in plant biology is to define the targets for ubiquitination, their interactors and their molecular function within the regulatory context.
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The ubiquitin–Proteasome System: central modifier of plant signalling
The New phytologist, 2012Co-Authors: Ari Sadanandom, Jack Lee, Mark Bailey, Richard Ewan, Stua NelisAbstract:Contents Summary 13 I. Brief history 13 II. Components of the ubiquitin–Proteasome System 14 III. Ubiquitin-mediated degradation: a recurrent theme in the plant life cycle 18 IV. Conclusion and future prospects 25 Acknowledgements 25 References 25 Summary Ubiquitin is well established as a major modifier of signalling in eukaryotes. However, the extent to which plants rely on ubiquitin for regulating their lifecycle is only recently becoming apparent. This is underlined by the over-representation of genes encoding ubiquitin-metabolizing enzymes in Arabidopsis when compared with other model eukaryotes. The main characteristic of ubiquitination is the conjugation of ubiquitin onto lysine residues of acceptor proteins. In most cases the targeted protein is rapidly degraded by the 26S Proteasome, the major proteolysis machinery in eukaryotic cells. The ubiquitin–Proteasome System is responsible for removing most abnormal peptides and short-lived cellular regulators, which, in turn, control many processes. This allows cells to respond rapidly to intracellular signals and changing environmental conditions. This review maps out the roles of the components of the ubiquitin–Proteasome System with emphasis on areas where future research is urgently needed. We provide a flavour of the diverse aspects of plant lifecycle where the ubiquitin–Proteasome System is implicated. We aim to highlight common themes using key examples that reiterate the importance of the ubiquitin–Proteasome System to plants. The future challenge in plant biology is to define the targets for ubiquitination, their interactors and their molecular function within the regulatory context.
