Opendata, web and dolomites

CsnCRL SIGNED

The molecular basis of CULLIN E3 ligase regulation by the COP9 signalosome

Total Cost €

0

EC-Contrib. €

0

Partnership

0

Views

0

 CsnCRL project word cloud

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

cryo    signalosome    physiology    forms    post    humans    ubiquitin    repertoire    functional    divided    translational    modifications    complexes    gt    mechanism    independent    maintains    multiple    combined    cullin    additional    isopeptidase    crystallography    bound    200    molecular    cop9    regulated    regulation    ring    auto    eight    e3    nedd8    subunit    covalently    isolated    domain    constituent    cleavage    vast    reveal    erc    13    diverse    proteasome    ligases    insights    constituting    cell    atomic    action    crl    receptor    inactive    removes    bind    substrate    assembly    modules    principles    ray    binds    proteins    normal    30    crucially    microscopy    mediate    largely    integrity    biochemistry    subunits    adaptor    protective    electron    families    lingaraju    csn    attached    interdisciplinary    combining    al    ubiquitination    nature    2011    intend    designed    collectively    itself    specificity    prevents    structurally    structures    e3s    destructive    subject    deneddylates    et    structural    resolution    fischer    degraded    2014    vivo    20    vitro    underlying    protein    function    biology    conferred    activator    pursue    crls    lab    seven   

Project "CsnCRL" data sheet

The following table provides information about the project.

Coordinator
FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH FONDATION 

Organization address
address: MAULBEERSTRASSE 66
city: BASEL
postcode: 4058
website: www.fmi.ch

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 Switzerland [CH]
 Total cost 2˙200˙677 €
 EC max contribution 2˙200˙677 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-ADG
 Funding Scheme ERC-ADG
 Starting year 2016
 Duration (year-month-day) from 2016-01-01   to  2020-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH FONDATION CH (BASEL) coordinator 2˙200˙677.00

Map

 Project objective

Specificity in the ubiquitin-proteasome system is largely conferred by ubiquitin E3 ligases (E3s). Cullin-RING ligases (CRLs), constituting ~30% of all E3s in humans, mediate the ubiquitination of ~20% of the proteins degraded by the proteasome. CRLs are divided into seven families based on their cullin constituent. Each cullin binds a RING domain protein, and a vast repertoire of adaptor/substrate receptor modules, collectively creating more than 200 distinct CRLs. All CRLs are regulated by the COP9 signalosome (CSN), an eight-protein isopeptidase that removes the covalently attached activator, NEDD8, from the cullin. Independent of NEDD8 cleavage, CSN forms protective complexes with CRLs, which prevents destructive auto-ubiquitination.

The integrity of the CSN-CRL system is crucially important for the normal cell physiology. Based on our previous work on CRL structures (Fischer, et al., Nature 2014; Fischer, et al., Cell 2011) and that of isolated CSN (Lingaraju et al., Nature 2014), We now intend to provide the underlying molecular mechanism of CRL regulation by CSN. Structural insights at atomic resolution, combined with in vitro and in vivo functional studies are designed to reveal (i) how the signalosome deneddylates and maintains the bound ligases in an inactive state, (ii) how the multiple CSN subunits bind to structurally diverse CRLs, and (iii) how CSN is itself subject to regulation by post-translational modifications or additional further factors.

The ERC funding would allow my lab to pursue an ambitious interdisciplinary approach combining X-ray crystallography, cryo-electron microscopy, biochemistry and cell biology. This is expected to provide a unique molecular understanding of CSN action. Beyond ubiquitination, insight into this >13- subunit CSN-CRL assembly will allow examining general principles of multi-subunit complex action and reveal how the numerous, often essential, subunits contribute to complex function.

 Publications

year authors and title journal last update
List of publications.
2016 Georg Petzold, Eric S. Fischer, Nicolas H. Thomä
Structural basis of lenalidomide-induced CK1α degradation by the CRL4CRBN ubiquitin ligase
published pages: 127-130, ISSN: 0028-0836, DOI: 10.1038/nature16979
Nature 532/7597 2019-07-02
2017 Stefano Mattarocci, Julia K Reinert, Richard D Bunker, Gabriele A Fontana, Tianlai Shi, Dominique Klein, Simone Cavadini, Mahamadou Faty, Maksym Shyian, Lukas Hafner, David Shore, Nicolas H Thomä, Ulrich Rass
Rif1 maintains telomeres and mediates DNA repair by encasing DNA ends
published pages: 588-595, ISSN: 1545-9993, DOI: 10.1038/nsmb.3420
Nature Structural & Molecular Biology 24/7 2019-07-02
2016 Simone Cavadini, Eric S. Fischer, Richard D. Bunker, Alessandro Potenza, Gondichatnahalli M. Lingaraju, Kenneth N. Goldie, Weaam I. Mohamed, Mahamadou Faty, Georg Petzold, Rohan E. J. Beckwith, Ritesh B. Tichkule, Ulrich Hassiepen, Wassim Abdulrahman, Radosav S. Pantelic, Syota Matsumoto, Kaoru Sugasawa, Henning Stahlberg, Nicolas H. Thomä
Cullin–RING ubiquitin E3 ligase regulation by the COP9 signalosome
published pages: 598-603, ISSN: 0028-0836, DOI: 10.1038/nature17416
Nature 531/7596 2019-07-02
2018 Quinlan L. Sievers, Georg Petzold, Richard D. Bunker, Aline Renneville, Mikołaj Słabicki, Brian J. Liddicoat, Wassim Abdulrahman, Tarjei Mikkelsen, Benjamin L. Ebert, Nicolas H. Thomä
Defining the human C2H2 zinc finger degrome targeted by thalidomide analogs through CRBN
published pages: eaat0572, ISSN: 0036-8075, DOI: 10.1126/science.aat0572
Science 362/6414 2019-03-27

Are you the coordinator (or a participant) of this project? Plaese send me more information about the "CSNCRL" project.

For instance: the website url (it has not provided by EU-opendata yet), the logo, a more detailed description of the project (in plain text as a rtf file or a word file), some pictures (as picture files, not embedded into any word file), twitter account, linkedin page, etc.

Send me an  email (fabio@fabiodisconzi.com) and I put them in your project's page as son as possible.

Thanks. And then put a link of this page into your project's website.

The information about "CSNCRL" are provided by the European Opendata Portal: CORDIS opendata.

More projects from the same programme (H2020-EU.1.1.)

PLAT_ACE (2019)

A new platform technology for the on-demand access to large acenes

Read More  

SoftHandler (2019)

Commercial feasibility of an integrated soft robotic system for industrial handling

Read More  

LO-KMOF (2019)

Vapour-deposited metal-organic frameworks as high-performance gap-filling dielectrics for nanoelectronics

Read More