Objective
The concept of the proteostasis network (PN) represent a systems biology approach to protein deposition diseases (e.g. neurodegenerative diseases, amyloidoses, type II diabetes). The PN includes all the cellular components involved in the synthesis, folding, and degradation of proteins, as well as the regulatory mechanisms required for maintaining a functioning proteome despite cellular stress, mutations, or protein misfolding.
When the misfolded protein load exceeds the capacity of the PN to maintain, protein aggregation can occur. Protein misfolding and subsequent aggregation is already thought to be the main cause of neuronal death in neurodegenerative diseases. Our study on the aggregation of p53, however, is the first report of protein aggregation leading directly to increased cell proliferation of the same cell in which the aggregation occurs by a gain of function mechanism.
p53 is a potent tumor suppressor, and it is the most frequently mutated gene in human cancer (approximately half of the cases). We observed that mutant p53 not only strongly aggregated in tumor cells, - thereby already eliminating one copy of p53 – but that it also co-aggregated in a dominant negative way with wild type p53 and its paralogs, p63 and p73, sequestering these tumor suppressors that are pivotal to prevent tumorigenesis.
The ability of the PN to cope with mutant or damaged biological material varies with the differentiation stage of cells, as well as deteriorates with cellular senescence. According to our hypothesis, the decline of the PN, particularly its decreasing ability to control aggregation-prone mutant p53 proteins, is one of the contributing factors to the steadily increasing incidence of cancer with age.
We are proposing to study the aggregation of mutant p53 proteins in undifferentiated, differentiated, and senescent cells to test our hypothesis and gain information on the key factors keeping p53 aggregation, and tumorigenesis, at bay.
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 biological sciences molecular biology structural biology
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Programme(s)
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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.
FP7-PEOPLE-2011-IIF
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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
9052 ZWIJNAARDE - GENT
Belgium
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.