Objective
"Ubiquitin E3 enzymes participate in the last step of a three-enzyme cascade, where they transfer ubiquitin from E2 enzymes to substrates, therefore are responsible to bring the right substrate to the right E2 enzyme. The tripartite motif (TRIM) family of ubiquitin E3 ligases includes 70 members that are involved in cellular processes such as immune signaling, transcriptional regulation and apoptosis. Defects in TRIM E3 ligase activity have been linked to cancer and developmental and genetic diseases. Despite TRIM vital roles, important aspects of their mechanism as E3 ligases remain unknown mainly due to their multi-domain architecture, their ability to self-associate into dimers and higher order complexes, and their ability to serve as E3 ligases not only for ubiquitin but also for ubiquitin-like proteins. We will pursue our interest in the molecular mechanism of TRIM E3 activity by working on TRIM25 that possesses dual E3 activity for ubiquitin and ubiquitin-like protein ISG15. We will determine the molecular mechanism of TRIM25 E3 activity using molecular biology, cell biology, crystallography and biochemistry. Specifically, we will map the contribution of TRIM25 different domains and the oligomineric state to its E3 activity. Then, together with crystal structures of TRIM25 with its cognate E2, UBCH8, charged with ubiquitin or ISG15, we will provide structural insight on how TRIM25 works in concert with UBCH8 and possesses dual E3 activity. In addition, we will determine how TRIM25 interacts with its substrate, 14-3-3σ, and whether the oligomeric state is important for substrate binding. Since 14-3-3σ undergoes ubiquitination and ISGylation by TRIM25 we will investigate the potential crosstalk between modifications. Specifically, we will test for the formation of mixed ubiquitin-ISG15 chains. Our work will provide mechanistic details on TRIM E3 ligase activity as well as critical data for future research on TRIM proteins as targets for therapeutic drug design."
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciences basic medicine medicinal chemistry
- natural sciences earth and related environmental sciences geology mineralogy crystallography
- natural sciences biological sciences cell biology
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
- natural sciences biological sciences molecular biology
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
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-2013-CIG
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.
MC-CIG - Support for training and career development of researcher (CIG)
Coordinator
91904 JERUSALEM
Israel
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.