19 research outputs found

    Intracellular Trafficking of Guanylate-Binding Proteins Is Regulated by Heterodimerization in a Hierarchical Manner

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    Guanylate-binding proteins (GBPs) belong to the dynamin family of large GTPases and represent the major IFN-Îł-induced proteins. Here we systematically investigated the mechanisms regulating the subcellular localization of GBPs. Three GBPs (GBP-1, GBP-2 and GBP-5) carry a C-terminal CaaX-prenylation signal, which is typical for small GTPases of the Ras family, and increases the membrane affinity of proteins. In this study, we demonstrated that GBP-1, GBP-2 and GBP-5 are prenylated in vivo and that prenylation is required for the membrane association of GBP-1, GBP-2 and GBP-5. Using co-immunoprecipitation, yeast-two-hybrid analysis and fluorescence complementation assays, we showed for the first time that GBPs are able to homodimerize in vivo and that the membrane association of GBPs is regulated by dimerization similarly to dynamin. Interestingly, GBPs could also heterodimerize. This resulted in hierarchical positioning effects on the intracellular localization of the proteins. Specifically, GBP-1 recruited GBP-5 and GBP-2 into its own cellular compartment and GBP-5 repositioned GBP-2. In addition, GBP-1, GBP-2 and GBP-5 were able to redirect non-prenylated GBPs to their compartment in a prenylation-dependent manner. Overall, these findings prove in vivo the ability of GBPs to dimerize, indicate that heterodimerization regulates sub-cellular localization of GBPs and underscore putative membrane-associated functions of this family of proteins

    Survivin, a molecular target for therapeutic interventions in squamous cell carcinoma

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    Tackling Invasive Alien Species in Europe II: Threats and Opportunities Until 2020

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    Invasive alien species (IAS) are a significant and growing problem worldwide. In Europe, some aspects of IAS have been addressed through existing legal instruments, but these are far from sufficient to tackle the problem comprehensively. The FINS II Conference considered the relevance of Top 20 IAS issues (Top 10 threats and opportunities) for Europe determined at the 1st Freshwater Invasiveness-Networking for Strategy (FINS I) conference held in Ireland in 2013. Using a similar format of sequential group voting, threats from FINS I (lack of funding, of awareness and education; poor communication) and several new threats (lack of lead agencies, of standardized management and of common approach; insufficient monitoring and management on private property) were identified by 80 academics, applied scientists, policy makers and stakeholders from 14 EU and three non-EU countries (including 10 invited speakers) during four workshop break-out sessions (legislation remit in both EU/non-EU countries; best management and biosecurity practice for control; data management and early warning; pathways of introductions and citizen science). Identified opportunities include improved cooperation and communication, education and leadership to enhance public awareness and stakeholder participation, systems establishment for early detection, rapid response, monitoring and management of IAS using standardised methods of data collection, storage and usage. The sets of threats and opportunities identified underline the importance of international cooperation on IAS issues in communication, education and funding as priorities, as well as in standardization of legislation, control methods and best practise of research.WoSScopu
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