NEDD8ANDCRLLIGASES
Regulation and Function of Cullin-Ring E3 ubiquitin ligases and the Nedd8 ubiquitin-like protein modification system
| Coordinatore | UNIVERSITY OF DUNDEE
Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie. |
| Nazionalità Coordinatore | United Kingdom [UK] |
| Totale costo | 1˙397˙676 € |
| EC contributo | 1˙397˙676 € |
| Programma | FP7-IDEAS-ERC
Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
| Code Call | ERC-2009-StG |
| Funding Scheme | ERC-SG |
| Anno di inizio | 2009 |
| Periodo (anno-mese-giorno) | 2009-11-01 - 2014-10-31 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
UNIVERSITY OF DUNDEE
Organization address
address: Nethergate contact info |
UK (DUNDEE) | hostInstitution | 1˙397˙676.60 |
| 2 |
UNIVERSITY OF DUNDEE
Organization address
address: Nethergate contact info |
UK (DUNDEE) | hostInstitution | 1˙397˙676.60 |
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Obiettivo del progetto (Objective)
'Cullin-RING E3 ubiquitin ligases (CRLs) are multi-subunit enzyme complexes that catalyze isopeptide bond formation between the C-terminal glycine residue of the small protein ubiquitin and lysine residues of substrate proteins (ubiquitination). Multiple rounds of ubiquitination lead to the formation of ubiquitin chains, which are recognized by the 26S-proteasome, a protease that degrades the substrates. Targeted protein degradation by CRLs is an important part of many essential cellular processes. Progression of the cell cycle, for example, requires CRL-dependent ubiquitination and degradation of cyclin-dependent kinase inhibitors (CKIs). Clearly, substrate ubiquitination needs to occur at the right time and place, and it is thus essential that CRL activity is tightly regulated. In fact, the malfunction of CRLs has been associated with many human diseases, including cancer. One mode of CRL regulation is the activation of the ligase by the small ubiquitin-like molecule Nedd8 (neddylation). Neddylation of the cullin triggers the formation of an active ligase complex and induces structural changes that allow efficient substrate ubiquitination. My proposal aims at gaining mechanistic insights into the activation and inactivation cycles of CRL complexes. I propose to study the regulation of cullin neddylation and the role of the newly identified Nedd8 E3 ligase Dcn1 in this process. I will identify new substrates of the Nedd8 pathway with yeast genetics and biochemistry and generate a systems-wide map of genetic interactions with CRL substrates and regulators using synthetic genetic array (SGA) analysis.'