Objective
The smooth action of signal transduction cascades is essential prerequisite for higher organisms, and failure here is the major cause of cancer. Crucial for these cascades is assistance by the molecular chaperone Hsp90. It supports protein folding for a su bset of proteins, most of which are oncogenes, and is a cancer drug target itself. Just over 100 substrates are identified to date, more than 50 are kinases, but the specific folding problem of kinases is elusive. We will focus on Cdk kinases, which contro l the cell cycle. They are a homologous family, some of its members require Hsp90, others do not. We set out to establish a new innovative concept to this fundamental question of explaining Hsp90 specificity by selective modulation of kinase stability. We use a multidisciplinary approach combining biopysics, biochemistry and cell biology, applying advanced protein engineering techniques and cutting edge NMR spectroscopy.First we will analyse the stability of Hsp90-dependent and independent Cdk kinases for full length proteins, kinase domains and fragments thereof, and we will test whether their activation or inactivation influences stability. Second, we will determine under which conditions Cdks bind to Hsp90. We will analyse whether activation processes an d stability influence Hsp90 binding. Third, we want to determine the conformation of Cdk kinase in the Hsp90-bound state. We will map the binding site of Hsp90 in Cdks, and we will follow the kinase's structure throughout the Hsp90 chaperone cycle. Fourth, we will map the binding site of the kinase substrate within Hsp90 and monitor its conformational changes. Finally, we will go into the living cell to identify the structural elements that affect stability of Cdk kinases in vivo. We expect to provide a new paradigm for the chaperoning of oncogenic kinases that will inspire basic research and delivers vital progress for cancer studies.'
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.
- medical and health sciences basic medicine neurology dementia alzheimer
- natural sciences biological sciences cell biology
- natural sciences physical sciences optics spectroscopy absorption spectroscopy
- natural sciences biological sciences biochemistry biomolecules proteins protein folding
- medical and health sciences clinical medicine oncology
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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.
FP6-2004-MOBILITY-8
See other projects for this call
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
UTRECHT
Netherlands
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.