Objective
Targeted protein degradation has emerged as a major regulator of many essential cellular processes. Consistent with these findings, a wide variety of human diseases have been linked to defects in the cells protein degradation machinery. Ubiquitin-dependent protein degradation has been identified as the major player governing this process. Ubiquitin is a small polypeptide that gets linked to other proteins through the actions of an enzymatic cascade consisting of an E1 activating- and E2 conjugating enzyme, as well as an E3 ubiquitin ligase. Once proteins are tagged with a chain of ubiquitin molecules, they are degraded by the 26S proteasome.
The E3 ligases are of significant importance for this process, since they recognize the substrate prior to ubiquitination. Here I propose to study one subclass of E3 enzymes, the multi-subunit SCF E3 ubiquitin ligase complexes. One core component of these complexes are cullin proteins, which serve as a scaffold for the recruitment of E2-bound ubiquitin and the substrate by other ligase subunits. Additionally, positive regulation of E3 ligase activity is achieved by modifying this cullin subunit with the ubiquitin-like molecule Nedd8/Rub1p (neddylation).
SCF ubiquitin ligases and Nedd8 modification of the cullin sub unit are highly conserved throughout evolution, including in humans. While the importance of neddylation has been demonstrated across species, the precise molecular mechanisms that regulate this process remain elusive. I have identified a novel and conserved protein required for cullin modification in budding yeast and C. elegans. My preliminary data suggests that this protein is a component of the Nedd8 modification machinery and might possibly act as a ligase for Nedd8. The goal of this proposal is to further characterize this protein, to determine its Nedd8 ligase activity by in vivo and in vitro reconstitution assays, and to find novel players in this pathway using biochemical and genetic approaches.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- engineering and technology materials engineering crystals
- natural sciences mathematics pure mathematics mathematical analysis functional analysis
- natural sciences chemical sciences organic chemistry amines
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP6-2002-MOBILITY-5
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
ZURICH
Switzerland
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.