Objective
Background: In differentiating cells, translation of many mRNAs encoding late-acting proteins issilenced until these proteins are needed. During terminal differentiation of erythrocytes, 15-Lipoxygenase (LOX) protein expression is regulated by a specific s equence element ('DICE') in the 3'untranslated region (UTR) of its mRNA. Previous work from the Hentze lab has shown that the RNAbinding proteins hnRNP K and E1 bind to the DICE in vivo and in vitro, inhibiting translation at the 60Sribosomal subunit joini ng step by an unknown mechanism.Objective: Our objective is to determine the precise molecular mechanism of action of the LOX/DICE3'UTR silencing complex by identifying the functional and physical links that connect the complex tothe initiating ribosome. W e will test two major hypotheses: (1) silencing requires specific molecularinteractions between hnRNPK/E1 and an initiation factor mediating subunit joining or (2) it requiresinteraction with a specific ribosomal structure, and this interaction inhibits su bunit joining.Approach: To identify functional targets of the DICE complex, a reconstituted in vitro translation initiationassay will be adapted to study DICE-mediated silencing. With this system, we will test the hypothesisthat the DICE complex inhibits s ubunit joining by modulating the activity and/or association of specifictranslation initiation factors. To identify specific molecular contacts made by and required for DICE-mediated silencing we will use two complementary approaches: (1) structure-guided site-specificmutagenesis approaches, followed by analysis in established cell culture and in vitro assays; (2) affinity-directed mass spectrometry ('functional proteomics') to directly identify interactions.Medical Relevance: Inappropriate control of gene expression in general, and of tumor suppressorgenes and oncogenes in particular, is a major component in molecular etiology of cancer. Aberrant#'
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 proteomics
- medical and health sciences clinical medicine oncology
- natural sciences chemical sciences analytical chemistry mass spectrometry
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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-7
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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.
IIF - Marie Curie actions-Incoming International Fellowships
Coordinator
HEIDELBERG
Germany
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.