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DUBs26S SIGNED

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

Total Cost €

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EC-Contrib. €

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Partnership

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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.

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

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

 Partnership

Take a look of project's partnership.

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

Map

 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

year authors and title journal last update
List of publications.
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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