EU H2020 Project "DUBS26S (Role of a novel proteasome-associated DUB – A boon for therapeutics)": description, partecipants, costs and EC-fundings

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DUBs26S project word cloud

Explore the words cloud of the DUBs26S project. It provides you a very rough idea of what is the project "DUBs26S" about.

clearing phyla myriad extraordinarily drugable replacing live competencies networking proteins interaction enzymes active tools ensures msc cancers embark deubiquitinating proposing tweaks fits static msca subset notion usp9x relevance training usp14 independent career strategies preparation goals respective labs enzyme uch proposes drug association spheres reported redundant tissue expanded enzymatic clinically span fact shatters efforts eukaryotic relationship committed action fruition instigate substrate applicative alter clinical basic human complexes investigation researcher realign dubs host cells life largely embellished subunit composition opens ubiquitin fixed 26s purified proteasome search found incorporation disposal processivity crux structure specificity reciprocal unravel job neurodegeneration l5 multisubunit experimental site conserved dub healthy

Project "DUBs26S" data sheet

The following table provides information about the project.

Coordinator	TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY Organization address address: SENATE BUILDING TECHNION CITY city: HAIFA postcode: 32000 website: www.technion.ac.il contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.
Coordinator Country	Israel [IL]
Total cost	182˙509 €
EC max contribution	182˙509 € (100%)
Programme	1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
Code Call	H2020-MSCA-IF-2016
Funding Scheme	MSCA-IF-EF-ST
Starting year	2017
Duration (year-month-day)	from 2017-11-01 to 2019-10-31

#	participants	country	role	EC contrib. [€]
1	TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY	IL (HAIFA)	coordinator	182˙509.00

TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY

IL (HAIFA)

coordinator

182˙509.00

Project objective

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.

Publications

List of publications.
year	authors and title	journal	last update
2019	Indrajit Sahu, Sachitanand M Mali, Prasad Sulkshane, Andrey Rozenberg, Cong Xu, Roni Morag, Manisha Priyadarsini Sahoo, Sumeet K Singh, Zhanyu Ding, Yifan Wang, Sharleen Day, Yao Cong, Oded Kleifeld, Ashraf Brik, Michael H Glickman Signature activities of 20S proteasome include degradation of the ubiquitin-tag with the protein under hypoxia published pages: , ISSN: , DOI: 10.1101/2019.12.20.883942	BioRxIV	2020-01-29
2019	Zhanyu Ding, Cong Xu, Indrajit Sahu, Yifan Wang, Zhenglin Fu, Min Huang, Catherine C.L. Wong, Michael H. Glickman, Yao Cong Structural Snapshots of 26S Proteasome Reveal Tetraubiquitin-Induced Conformations published pages: , ISSN: 1097-2765, DOI: 10.1016/j.molcel.2019.01.018	Molecular Cell	2019-05-15

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