54 research outputs found
Specific inhibition of Mdm2-mediated neddylation by Tip60
No full textTip60 is a histone acetyl transferase ( HAT) and a cofactor of transcription, but also an interaction partner of the Mdm2 oncoprotein. The functional consequences of this interaction are only partially understood and were further explored in this study. We found that Tip60 is capable of selectively inhibiting the Mdm2mediated conjugation of Nedd8 to p53, whereas it did not affect p53 ubiquitination. In contrast, the known Mdm2 antagonist p14arf preferentially blocked Ubiquitin conjugation by Mdm2. To identify underlying mechanisms, we studied the intracellular localization of Tip60 and Mdm2. Both proteins relocalized each other to the PML nuclear bodies, but a similar localization pattern was observed even in the absence of PML. Analysis of Tip60 deletion mutants revealed that some mutants, while still interacting with Mdm2, failed to relocalize it and to inhibit Mdm2-mediated neddylation, suggesting that these two phenomena require biochemical activities in addition to the mere interaction between the two proteins. For both activities, the HAT domain of Tip60 was not required. We propose that Tip60 can act as a selective antagonist to Mdm2-mediated neddylation but not ubiquitination. Hence, the two different E3 ligase activities of Mdm2 can be regulated individually
Research in medical education - chances and challenges : international conference, 20th - 22nd May 2009, Heidelberg ; congress abstracts
No full textRole of STAT3 in glucocorticoid-induced expression of the human IL-10 gene
No full textIn the present report we have determined the molecular mechanisms, which govern the expression of the human IL-10 gene when induced by the glucocorticoid Methyl-Prednisolone (MP). Treatment of cells with MP at 10(-6) M will readily induce IL-10 in CD19+ primary B cells and in a human B cell line. Analysis of the IL-10 promoter showed a robust 18-fold induction and demonstrated that a potential GRE motif was not required, while mutation of the -120 STAT-motif strongly reduced MP-induced trans-activation. A strong induction was also seen with a trimeric STAT-motif and over-expression of dominant-negative STAT3 could block MP induction of IL-10 mRNA. Finally, MP treatment induced binding of STAT3 to the promoter as shown by gelshift, supershift and by chromatin-immunoprecipitation. These data show that glucocorticoid-induced expression of the IL-10 gene is mediated by the transcription factor STAT3
Specific inhibition of Mdm2-mediated neddylation by Tip60
No full text Udgivelsesdato: 2007-Oct-16Tip60 is a histone acetyl transferase (HAT) and a cofactor of transcription, but also an interaction partner of the Mdm2 oncoprotein. The functional consequences of this interaction are only partially understood and were further explored in this study. We found that Tip60 is capable of selectively inhibiting the Mdm2- mediated conjugation of Nedd8 to p53, whereas it did not affect p53 ubiquitination. In contrast, the known Mdm2 antagonist p14arf preferentially blocked Ubiquitin conjugation by Mdm2. To identify underlying mechanisms, we studied the intracellular localization of Tip60 and Mdm2. Both proteins relocalized each other to the PML nuclear bodies, but a similar localization pattern was observed even in the absence of PML. Analysis of Tip60 deletion mutants revealed that some mutants, while still interacting with Mdm2, failed to relocalize it and to inhibit Mdm2-mediated neddylation, suggesting that these two phenomena require biochemical activities in addition to the mere interaction between the two proteins. For both activities, the HAT domain of Tip60 was not required. We propose that Tip60 can act as a selective antagonist to Mdm2-mediated neddylation but not ubiquitination. Hence, the two different E3 ligase activities of Mdm2 can be regulated individuall
Specific inhibition of Mdm2-mediated neddylation by Tip60
No full text Udgivelsesdato: 2007-Oct-16Tip60 is a histone acetyl transferase (HAT) and a cofactor of transcription, but also an interaction partner of the Mdm2 oncoprotein. The functional consequences of this interaction are only partially understood and were further explored in this study. We found that Tip60 is capable of selectively inhibiting the Mdm2- mediated conjugation of Nedd8 to p53, whereas it did not affect p53 ubiquitination. In contrast, the known Mdm2 antagonist p14arf preferentially blocked Ubiquitin conjugation by Mdm2. To identify underlying mechanisms, we studied the intracellular localization of Tip60 and Mdm2. Both proteins relocalized each other to the PML nuclear bodies, but a similar localization pattern was observed even in the absence of PML. Analysis of Tip60 deletion mutants revealed that some mutants, while still interacting with Mdm2, failed to relocalize it and to inhibit Mdm2-mediated neddylation, suggesting that these two phenomena require biochemical activities in addition to the mere interaction between the two proteins. For both activities, the HAT domain of Tip60 was not required. We propose that Tip60 can act as a selective antagonist to Mdm2-mediated neddylation but not ubiquitination. Hence, the two different E3 ligase activities of Mdm2 can be regulated individuall
Louise Westmarland, \u3ci\u3eGender and Policing: Sex, Power, and Police Culture\u3c/i\u3e
No full textOriginally released in 2001, Louise Westmarland’s Gender and Policing has been released with a new publisher. With Routledge’s rerelease of the book, it is necessary to reassess the value of its research in the field of gender and policing to determine if it is still relevant. Throughout the book, Westmarland uses qualitative data to explore gendered themes in United Kingdom police forces. More specifically, her work focuses on whether differential deployment exists in policing based on gender and explores the role of gender within policing culture in several different situations. To analyze possible gendered patterns, Westmarland bases her work on two case studies: One on a rural police force of about 1,300 officers, and one on a metropolitan police force of about 3,000 officers. In addition to the six months of ride-alongs and participant observations in each force, the author conducted in-depth interviews with over 35 officers and focus groups with an additional 35 officers
La genèse de la pensée politique de Rousseau d'après sa correspondance (1730-1762)
No full textLa lettre, " miroir de l'âme " apparaît au 18eme siècle français comme le meilleur outil de communication. Elle permet de découvrir l'état social et psychologique de son auteur dans toute son intimité. A ce niveau se situe l'importance de l'étude consacrée à la genèse de la pensée politique de Rousseau d'après sa correspondance. Il s'agit de reconstituer l'évolution de la pensée politique de cet auteur, d'après les relations qu'il a entretenues avec son entourage de sa sortie de Genève en 1728 à sa fuite de Montmorency en 1762. Ainsi, les séjours de Rousseau en Savoie, à Paris, à Venise et à Montmorency, offrent des renseignements favorables à l'éveil de sa pensée politique. L'antagonisme et la convivialité qui ont caractérisé sa vie, donnent un éclat particulier à l'appréhension des problèmes sociaux et politiques auxquels il est confronté. La correspondance établit clairement que sa fierté, les échecs de ses projets et le regard critique qu'il jette sur les Lumières sont autant de facteurs de sa conscience politique. A force de vivre l'expérience de la pauvreté, de l'amitié et de la protection, de l'injustice des hommes, Rousseau est devenu écrivain politique. Outre les Confessions, la Correspondance le montre un ambitieux à l'excès, une sorte de Rastignac ou de Julien Sorel sorti de Genève pour la conquête de Paris.The letter, "mirror of the soul" seems to the 18-th century French as the best tool of communication. She allows to discover the social and psychological state of her author in all her intimacy. At this level is situated the importance of the study dedicated to the genesis of the political thought of Rousseau according to its correspondence. It is a question of reconstituting the evolution of the political thought of this author, according to the relations which he maintained with his circle of acquaintances of his exit of Geneva in 1728 in his flight of Montmorency in 1762. So, Rousseau's stays in Savoy, in Paris, in Venice and in Montmorency, give favorable information to the awakening of the political thought. Antogonism and conviviality wich characterized its life, give a particular brightness to the apprehension of the social and political problems with which it is confronted. Correspondence establishes clearly that his pride, the failures of the projects and the critical glance which it throws on lights are so many factors of its political consciousness. Due to living the experience of the poverty, the friendship and the protection, the injustice of the people, Rousseau became political writer. Besides Confessions, Correspondence shows him an ambitious to the excess, a sort of Rastignac or Julien Sorel taken out of Geneva for the conquest of Paris.ORLEANS-BU Lettres (452342103) / SudocSudocFranceF
CO2 Isotopic Composition in the Upper Troposphere: the Project CARIBIC
No full textManuscript describes the project CARIBIC (Civil Aircraft for the Regular Investigation of the atmosphere Based on an Instrument Container) and its approach of air sampling and CO2 isotope measurements by using a commercial aircraft (flights at ~ 10 km) as observational platform. In particular the paper focuses on possible sampling artefacts, on the troposphere-stratosphere mixing, effects which can specifically modify CO2 isotope composition and gives examples of CO2 isotope composition in the upper troposphere. The results to be presented in the manuscript have been obtained earlier, by measurements done at the Max Planck Institute for Chemistry, Mainz, Germany.JRC.D.4 - Isotope measurement
Detection of Moving Targets using Coherent Optical Frequency Domain Reflectometry
No full textWe present Doppler-corrected position and velocity measurement with a fiber-coupled COFDR system based on the FMCW radar principle for high precision localization applications. A high measurement accuracy and the ability to track targets are demonstrated
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