Objective
The misfolded, unfolded or unassembled proteins in the Endoplasmic Reticulum (ER) are degraded by the “Protein Quality Control Mechanism” named as ER-associated degradation (ERAD). In addition to its safeguard role, ERAD can regulate physiological processes that occur in the ER, for example degradation of HMG–CoA reductase, the key enzyme of cholesterol synthesis. ERAD is a multistep process, which starts with substrate (unwanted protein) selection followed by ubiquitination, retrotranslocation, deglycosylation and proteasomal degradation. Aberrant ERAD has implications on several diseases, such as cystic fibrosis, a1-antitrypsin (AAT) deficiency, diabetes, neurodegenerative diseases and cancer.
The details of ERAD mechanism are very well known through the studies in S.cerevisiae. Although the general scheme of the pathway is similar, ERAD is more complicated and highly regulated in mammals than in yeast. Studies in yeast suggested existence specialized ERAD pathways depending on the feature of the protein. These pathways are: ERAD-C ( for cytoplasmic misfolded domains), ERAD-L (for luminal misfolded regions), ERAD-M (for membrane misfolded regions). So far, this issue has not been studied in mammalian cells. Here, we intend to identify substrate specific differences present in retrotranslocation machineries in mammalian ERAD using four substrates with different structural features. Additionally, the effect of SVIP (the first identified endogenous ERAD inhibitor) on these substrates, the role of Npl4 in gp78-mediated ERAD and possible functional interaction of gp78 and hHrd1 enzymes will be examined.
This research will provide the first information on the substrate specific differences of mammalian ERAD, and also the functional interaction between two important ER-resident E3s: gp78 and Hrd1. Our results on substrate specific ERAD mechanism would contribute to the studies on the therapies of diseases such as cystic fibrosis and AAT deficiency.
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 clinical medicine endocrinology diabetes
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences zoology mammalogy
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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.
FP7-PEOPLE-IRG-2008
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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
35100 İzmir
Türkiye
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.