Record #203743 - GSI Repository

DUBs26S

Role of a novel proteasome-associated DUB – A boon for therapeutics

Coordinator	Technion – Israel Institute of Technology
Grant period	2017-11-01 - 2019-10-31
Funding body	European Union
Call number	H2020-MSCA-IF-2016
Grant number	748804
Identifier	G:(EU-Grant)748804

Note: Clearing-up old or redundant proteins is essential for cells to live; this job is largely done by 26S Proteasome. The multisubunit complex – 26S Proteasome – is extraordinarily conserved throughout all eukaryotic phyla, in terms of subunit composition and overall structure. However, in preparation of this research proposal, the Researcher found a novel association of 26S proteasome with a clinically important deubiquitinating enzyme (DUB), USP9X. In a subset of proteasome purified from human tissue by the Researcher, USP9X was in fact the major DUB replacing commonly reported enzymes (USP14, UCH-L5). This finding shatters the notion of proteasome as a static, fixed, complex, and opens up the search for expanded spheres of interaction. The crux of this MSC-IF action is the reciprocal relationship between 26S proteasome and USP9X. Using myriad experimental tools at his disposal, the Researcher proposes to unravel how this novel association tweaks each of their respective enzymatic properties. Incorporation of USP9X may alter substrate specificity and processivity of proteasome, as well as its own enzymatic properties. Even in the immediate term, this proposal will realign research efforts – both basic and applicative – towards USP9X as the new drugable target in the ubiquitin-proteasome system. This new enzymatic active site on proteasome complexes will instigate investigation into the cause of USP9X in neurodegeneration and various cancers. This MSCA-IF fits current European challenges to increase healthy life span by proposing strategies for drug design against DUBs of clinical relevance. Two host labs are committed to provide the Researcher with the best training and support to bring his research to fruition and embark his independent career. Novel experimental findings embellished with new technical competencies and networking experience ensures the Researcher’s future career goals.

Recent Publications

There are no publications

Record created 2017-06-14, last modified 2023-02-12

Similar records

Add to personal basket
Export as Author List with IDs BibTeX (UTF-8), EndNote XML, EndNote Text, RIS, MARC, Print MARC, MARCXML, DC,
Request correction
Submit fulltext

GSI Homepage \| GSI Library \| English Deutsch \| guest :: login GSI Repository
Search	Submit	Personalize Your alerts Your baskets Your searches	Help