The Experts below are selected from a list of 93336 Experts worldwide ranked by ideXlab platform
Jan A. Post - One of the best experts on this subject based on the ideXlab platform.
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The influence of reactive oxygen species on Cell Cycle Progression in mammalian Cells
Gene, 2012Co-Authors: Eline H. Verbon, Jan A. Post, Johannes BoonstraAbstract:Abstract Cell Cycle regulation is performed by cyclins and cyclin dependent kinases (CDKs). Recently, it has become clear that reactive oxygen species (ROS) influence the presence and activity of these enzymes and thereby control Cell Cycle Progression. In this review, we first describe the discovery of enzymes specialized in ROS production: the NADPH oxidase (NOX) complexes. This discovery led to the recognition of ROS as essential players in many Cellular processes, including Cell Cycle Progression. ROS influence Cell Cycle Progression in a context-dependent manner via phosphorylation and ubiquitination of CDKs and Cell Cycle regulatory molecules. We show that ROS often regulate ubiquitination via intermediate phosphorylation and that phosphorylation is thus the major regulatory mechanism influenced by ROS. In addition, ROS have recently been shown to be able to activate growth factor receptors. We will illustrate the diverse roles of ROS as mediators in Cell Cycle regulation by incorporating phosphorylation, ubiquitination and receptor activation in a model of Cell Cycle regulation involving EGF-receptor activation. We conclude that ROS can no longer be ignored when studying Cell Cycle Progression.
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molecular events associated with reactive oxygen species and Cell Cycle Progression in mammalian Cells
Gene, 2004Co-Authors: Johannes Boonstra, Jan A. PostAbstract:Cell Cycle Progression is regulated by a wide variety of external factors, amongst them are growth factors and extraCellular matrix factors. During the last decades evidence has been obtained that reactive oxygen species (ROS) may also play an important role in Cell Cycle Progression. ROS may be generated by external and internal factors. In this overview we describe briefly the generation of ROS and their effects on processes that have been demonstrated to play an essential role in Cell Cycle Progression, including such systems as signal transduction cascades, protein ubiquitination and degradation, and the cytoskeleton. These different effects of ROS influence Cell Cycle Progression dependent upon the amount and duration of ROS exposure. Activation of growth factor stimulated signaling cascades by low levels of ROS result in increased Cell Cycle Progression, or, in case of prolonged exposure, to a differentiation like growth arrest. From many studies it seems clear that the cyclin kinase inhibitor protein p21 plays a prominent role, leading to Cell Cycle arrest at higher but not directly lethal levels of ROS. Dependent upon the nature of p21 induction, the Cell Cycle arrest may be transient, coupled to repair processes, or permanent. At high concentrations of ROS all of the above processes are activated, in combination with enhanced damage to the building blocks of the Cell, leading to apoptosis or even necrosis.
Johannes Boonstra - One of the best experts on this subject based on the ideXlab platform.
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The influence of reactive oxygen species on Cell Cycle Progression in mammalian Cells
Gene, 2012Co-Authors: Eline H. Verbon, Jan A. Post, Johannes BoonstraAbstract:Abstract Cell Cycle regulation is performed by cyclins and cyclin dependent kinases (CDKs). Recently, it has become clear that reactive oxygen species (ROS) influence the presence and activity of these enzymes and thereby control Cell Cycle Progression. In this review, we first describe the discovery of enzymes specialized in ROS production: the NADPH oxidase (NOX) complexes. This discovery led to the recognition of ROS as essential players in many Cellular processes, including Cell Cycle Progression. ROS influence Cell Cycle Progression in a context-dependent manner via phosphorylation and ubiquitination of CDKs and Cell Cycle regulatory molecules. We show that ROS often regulate ubiquitination via intermediate phosphorylation and that phosphorylation is thus the major regulatory mechanism influenced by ROS. In addition, ROS have recently been shown to be able to activate growth factor receptors. We will illustrate the diverse roles of ROS as mediators in Cell Cycle regulation by incorporating phosphorylation, ubiquitination and receptor activation in a model of Cell Cycle regulation involving EGF-receptor activation. We conclude that ROS can no longer be ignored when studying Cell Cycle Progression.
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molecular events associated with reactive oxygen species and Cell Cycle Progression in mammalian Cells
Gene, 2004Co-Authors: Johannes Boonstra, Jan A. PostAbstract:Cell Cycle Progression is regulated by a wide variety of external factors, amongst them are growth factors and extraCellular matrix factors. During the last decades evidence has been obtained that reactive oxygen species (ROS) may also play an important role in Cell Cycle Progression. ROS may be generated by external and internal factors. In this overview we describe briefly the generation of ROS and their effects on processes that have been demonstrated to play an essential role in Cell Cycle Progression, including such systems as signal transduction cascades, protein ubiquitination and degradation, and the cytoskeleton. These different effects of ROS influence Cell Cycle Progression dependent upon the amount and duration of ROS exposure. Activation of growth factor stimulated signaling cascades by low levels of ROS result in increased Cell Cycle Progression, or, in case of prolonged exposure, to a differentiation like growth arrest. From many studies it seems clear that the cyclin kinase inhibitor protein p21 plays a prominent role, leading to Cell Cycle arrest at higher but not directly lethal levels of ROS. Dependent upon the nature of p21 induction, the Cell Cycle arrest may be transient, coupled to repair processes, or permanent. At high concentrations of ROS all of the above processes are activated, in combination with enhanced damage to the building blocks of the Cell, leading to apoptosis or even necrosis.
Burton B Yang - One of the best experts on this subject based on the ideXlab platform.
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foxo3 circular rna retards Cell Cycle Progression via forming ternary complexes with p21 and cdk2
Nucleic Acids Research, 2016Co-Authors: William W Du, Weining Yang, Zhenguo Yang, Preet Dhaliwal, Burton B YangAbstract:Most RNAs generated by the human genome have no protein-coding ability and are termed non-coding RNAs. Among these include circular RNAs, which include exonic circular RNAs (circRNA), mainly found in the cytoplasm, and intronic RNAs (ciRNA), predominantly detected in the nucleus. The biological functions of circular RNAs remain largely unknown, although ciRNAs have been reported to promote gene transcription, while circRNAs may function as microRNA sponges. We demonstrate that the circular RNA circ-Foxo3 was highly expressed in non-cancer Cells and were associated with Cell Cycle Progression. Silencing endogenous circ-Foxo3 promoted Cell proliferation. Ectopic expression of circ-Foxo3 repressed Cell Cycle Progression by binding to the Cell Cycle proteins cyclin-dependent kinase 2 (also known as Cell division protein kinase 2 or CDK2) and cyclin-dependent kinase inhibitor 1 (or p21), resulting in the formation of a ternary complex. Normally, CDK2 interacts with cyclin A and cyclin E to facilitate Cell Cycle entry, while p21works to inhibit these interactions and arrest Cell Cycle Progression. The formation of this circ-Foxo3-p21-CDK2 ternary complex arrested the function of CDK2 and blocked Cell Cycle Progression.
Jesper V Olsen - One of the best experts on this subject based on the ideXlab platform.
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uncovering sumoylation dynamics during Cell Cycle Progression reveals foxm1 as a key mitotic sumo target protein
Molecular Cell, 2014Co-Authors: Joost Schimmel, Karolin Eifler, Jon Otti Sigurðsson, Sabine A G Cuijpers, Ivo A Hendriks, Matty Verlaande Vries, Christian D Kelstrup, Chiara Francavilla, Rene H Medema, Jesper V OlsenAbstract:Loss of small ubiquitin-like modification (SUMOylation) in mice causes genomic instability due to the missegregation of chromosomes. Currently, little is known about the identity of relevant SUMO target proteins that are involved in this process and about global SUMOylation dynamics during Cell-Cycle Progression. We performed a large-scale quantitative proteomics screen to address this and identified 593 proteins to be SUMO-2 modified, including the Forkhead box transcription factor M1 (FoxM1), a key regulator of Cell-Cycle Progression and chromosome segregation. SUMOylation of FoxM1 peaks during G2 and M phase, when FoxM1 transcriptional activity is required. We found that a SUMOylation-deficient FoxM1 mutant was less active compared to wild-type FoxM1, implying that SUMOylation of the protein enhances its transcriptional activity. Mechanistically, SUMOylation blocks the dimerization of FoxM1, thereby relieving FoxM1 autorepression. Cells deficient for FoxM1 SUMOylation showed increased levels of polyploidy. Our findings contribute to understanding the role of SUMOylation during Cell-Cycle Progression.
Karolin Eifler - One of the best experts on this subject based on the ideXlab platform.
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SUMOylation-Mediated Regulation of Cell Cycle Progression and Cancer
Trends in Biochemical Sciences, 2015Co-Authors: Karolin Eifler, Alfred C. O. VertegaalAbstract:Protein conjugation with Small ubiquitin-like modifier (SUMOylation) has critical roles during Cell Cycle Progression. Many important Cell Cycle regulators, including many oncogenes and tumor suppressors, are functionally regulated via SUMOylation. The dynamic SUMOylation pattern observed throughout the Cell Cycle is ensured via distinct spatial and temporal regulation of the SUMO machinery. Additionally, SUMOylation cooperates with other post-translational modifications to mediate Cell Cycle Progression. Deregulation of these SUMOylation and deSUMOylation enzymes causes severe defects in Cell proliferation and genome stability. Different types of cancer were recently shown to be dependent on a functioning SUMOylation system, a finding that could be exploited in anticancer therapies.
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uncovering sumoylation dynamics during Cell Cycle Progression reveals foxm1 as a key mitotic sumo target protein
Molecular Cell, 2014Co-Authors: Joost Schimmel, Karolin Eifler, Jon Otti Sigurðsson, Sabine A G Cuijpers, Ivo A Hendriks, Matty Verlaande Vries, Christian D Kelstrup, Chiara Francavilla, Rene H Medema, Jesper V OlsenAbstract:Loss of small ubiquitin-like modification (SUMOylation) in mice causes genomic instability due to the missegregation of chromosomes. Currently, little is known about the identity of relevant SUMO target proteins that are involved in this process and about global SUMOylation dynamics during Cell-Cycle Progression. We performed a large-scale quantitative proteomics screen to address this and identified 593 proteins to be SUMO-2 modified, including the Forkhead box transcription factor M1 (FoxM1), a key regulator of Cell-Cycle Progression and chromosome segregation. SUMOylation of FoxM1 peaks during G2 and M phase, when FoxM1 transcriptional activity is required. We found that a SUMOylation-deficient FoxM1 mutant was less active compared to wild-type FoxM1, implying that SUMOylation of the protein enhances its transcriptional activity. Mechanistically, SUMOylation blocks the dimerization of FoxM1, thereby relieving FoxM1 autorepression. Cells deficient for FoxM1 SUMOylation showed increased levels of polyploidy. Our findings contribute to understanding the role of SUMOylation during Cell-Cycle Progression.