Objective
The components of the Cullin-RING Ligase (CRLs) E3 ubiquitin ligase family play key roles in a wide range of cellular processes including stress response, signal transduction, apoptosis and cell cycle progression, and accordingly, defects in their function and/or regulation are prominent in many pathologies including cancer. The modular CRL architecture is centred upon one of seven different cullin scaffold proteins which associate on one side with a RING protein that acts as receptor for an E2 ligase and, on the opposite side, with a substrate receptor (SR) that confers specificity to the complex. The multiplicity of SRs allows the recognition of many different substrates by the same CRL catalytic core. CRL-mediated ubiquitination modulates the substrate´s biological activity and in many cases targets them for proteasomal degradation. The COP9 signalosome (CSN) complex plays a fundamental role in CRL regulation both by forming stable inhibitory complexes with the CRLs where the E2 ligase and substrate binding sites are occluded, and by enzymatically removing Nedd8 (a homologue of ubiquitin) from the cullin scaffold subunit, in a process termed deneddylation, that leads to inactivation of CRLs. CRL regulation by CSN is still an incompletely understood topic mostly because of the lack of high resolution CSN/CRL structures due to the challenge that the crystallization of multi-protein assemblies of such complexity represents. Fortunately, recent technological developments in another structural technique, cryoelectron microscopy, now allow structure determination of relatively small protein complexes (< 500kDa) to near-atomic resolution. Hence, we propose to use this powerful technique to reveal very high-resolution structures of several different CSN/CRL holocomplexes and shed light on the mechanistic aspects of their function.
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.
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences physical sciences optics microscopy
- medical and health sciences clinical medicine oncology
- medical and health sciences basic medicine pathology
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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.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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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.
(opens in new window) H2020-MSCA-IF-2014
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
SW7 3RP London
United Kingdom
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.