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20SComplexity SIGNED

An integrative approach to uncover the multilevel regulation of 20S proteasome degradation

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EC-Contrib. €

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Project "20SComplexity" data sheet

The following table provides information about the project.

Coordinator
WEIZMANN INSTITUTE OF SCIENCE 

Organization address
address: HERZL STREET 234
city: REHOVOT
postcode: 7610001
website: www.weizmann.ac.il

contact info
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surname: n.a.
function: n.a.
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 Coordinator Country Israel [IL]
 Total cost 1˙500˙000 €
 EC max contribution 1˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-STG
 Funding Scheme ERC-STG
 Starting year 2015
 Duration (year-month-day) from 2015-04-01   to  2020-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    WEIZMANN INSTITUTE OF SCIENCE IL (REHOVOT) coordinator 1˙500˙000.00

Map

 Project objective

For many years, the ubiquitin-26S proteasome degradation pathway was considered the primary route for proteasomal degradation. However, it is now becoming clear that proteins can also be targeted for degradation by a ubiquitin-independent mechanism mediated by the core 20S proteasome itself. Although initially believed to be limited to rare exceptions, degradation by the 20S proteasome is now understood to have a wide range of substrates, many of which are key regulatory proteins. Despite its importance, little is known about the mechanisms that control 20S proteasomal degradation, unlike the extensive knowledge acquired over the years concerning degradation by the 26S proteasome. Our overall aim is to reveal the multiple regulatory levels that coordinate the 20S proteasome degradation route. To achieve this goal we will carry out a comprehensive research program characterizing three distinct levels of 20S proteasome regulation: Intra-molecular regulation- Revealing the intrinsic molecular switch that activates the latent 20S proteasome. Inter-molecular regulation- Identifying novel proteins that bind the 20S proteasome to regulate its activity and characterizing their mechanism of function. Cellular regulatory networks- Unraveling the cellular cues and multiple pathways that influence 20S proteasome activity using a novel systematic and unbiased screening approach. Our experimental strategy involves the combination of biochemical approaches with native mass spectrometry, cross-linking and fluorescence measurements, complemented by cell biology analyses and high-throughput screening. Such a multidisciplinary approach, integrating in vitro and in vivo findings, will likely provide the much needed knowledge on the 20S proteasome degradation route. When completed, we anticipate that this work will be part of a new paradigm – no longer perceiving the 20S proteasome mediated degradation as a simple and passive event but rather a tightly regulated and coordinated process.

 Publications

year authors and title journal last update
List of publications.
2020 Maya A. Olshina, Galina Arkind, Fanindra Kumar Deshmukh, Irit Fainer, Mark Taranavsky, Daniel Hayat, Shifra Ben-Dor, Gili Ben-Nissan, Michal Sharon
Regulation of the 20S Proteasome by a Novel Family of Inhibitory Proteins
published pages: 636-655, ISSN: 1523-0864, DOI: 10.1089/ars.2019.7816
Antioxidants & Redox Signaling 32/9 2020-04-15
2020 Shay Vimer, Gili Ben-Nissan, Michal Sharon
Direct characterization of overproduced proteins by native mass spectrometry
published pages: 236-265, ISSN: 1754-2189, DOI: 10.1038/s41596-019-0233-8
Nature Protocols 15/2 2020-04-15
2020 Maria G. Füzesi-Levi, Irit Fainer, Radoslav Ivanov Enchev, Gili Ben-Nissan, Yishai Levin, Meital Kupervaser, Gilgi Friedlander, Tomer Meir Salame, Reinat Nevo, Matthias Peter, Michal Sharon
CSNAP, the smallest CSN subunit, modulates proteostasis through cullin-RING ubiquitin ligases
published pages: 984-998, ISSN: 1350-9047, DOI: 10.1038/s41418-019-0392-8
Cell Death & Differentiation 27/3 2020-04-15
2018 Jelena Cveticanin, Ravit Netzer, Galina Arkind, Sarel J. Fleishman, Amnon Horovitz, Michal Sharon
Estimating Interprotein Pairwise Interaction Energies in Cell Lysates from a Single Native Mass Spectrum
published pages: 10090-10094, ISSN: 0003-2700, DOI: 10.1021/acs.analchem.8b02349
Analytical Chemistry 90/17 2019-11-22
2018 Dror S. Chorev, Tova Volberg, Ariel Livne, Miriam Eisenstein, Bruno Martins, Zvi Kam, Brigitte M. Jockusch, Ohad Medalia, Michal Sharon, Benny Geiger
Conformational states during vinculin unlocking differentially regulate focal adhesion properties
published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-018-21006-8
Scientific Reports 8/1 2019-11-22
2018 Gili Ben-Nissan, Shay Vimer, Shira Warszawski, Aliza Katz, Meital Yona, Tamar Unger, Yoav Peleg, David Morgenstern, Hadas Cohen-Dvashi, Ron Diskin, Sarel J. Fleishman, Michal Sharon
Rapid characterization of secreted recombinant proteins by native mass spectrometry
published pages: , ISSN: 2399-3642, DOI: 10.1038/s42003-018-0231-3
Communications Biology 1/1 2019-11-22
2019 Fanindra Kumar Deshmukh, Dana Yaffe, Maya A. Olshina, Gili Ben-Nissan, Michal Sharon
The Contribution of the 20S Proteasome to Proteostasis
published pages: 190, ISSN: 2218-273X, DOI: 10.3390/biom9050190
Biomolecules 9/5 2019-11-22
2018 Gili Ben-Nissan, Michal Sharon
The application of ion-mobility mass spectrometry for structure/function investigation of protein complexes
published pages: 25-33, ISSN: 1367-5931, DOI: 10.1016/j.cbpa.2017.10.026
Current Opinion in Chemical Biology 42 2019-06-05
2016 Gili Ben-Nissan, Almog Chotiner, Mark Tarnavsky, Michal Sharon
Structural Characterization of Missense Mutations Using High Resolution Mass Spectrometry: A Case Study of the Parkinson’s-Related Protein, DJ-1
published pages: 1062-1070, ISSN: 1044-0305, DOI: 10.1007/s13361-016-1379-z
Journal of The American Society for Mass Spectrometry 27/6 2019-06-05
2017 Gili Ben-Nissan, Mikhail E. Belov, David Morgenstern, Yishai Levin, Orly Dym, Galina Arkind, Carni Lipson, Alexander A. Makarov, Michal Sharon
Triple-Stage Mass Spectrometry Unravels the Heterogeneity of an Endogenous Protein Complex
published pages: 4708-4715, ISSN: 0003-2700, DOI: 10.1021/acs.analchem.7b00518
Analytical Chemistry 89/8 2019-06-05
2015 Shelly Rozen, Maria G. Füzesi-Levi, Gili Ben-Nissan, Limor Mizrachi, Alexandra Gabashvili, Yishai Levin, Shifra Ben-Dor, Miriam Eisenstein, Michal Sharon
CSNAP Is a Stoichiometric Subunit of the COP9 Signalosome
published pages: 585-598, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2015.09.021
Cell Reports 13/3 2019-06-05
2015 Oren Moscovitz, Gili Ben-Nissan, Irit Fainer, Dan Pollack, Limor Mizrachi, Michal Sharon
The Parkinson’s-associated protein DJ-1 regulates the 20S proteasome
published pages: 6609, ISSN: 2041-1723, DOI: 10.1038/ncomms7609
Nature Communications 6 2019-06-05
2015 Dror S. Chorev, Gili Ben-Nissan, Michal Sharon
Exposing the subunit diversity and modularity of protein complexes by structural mass spectrometry approaches
published pages: 2777-2791, ISSN: 1615-9853, DOI: 10.1002/pmic.201400517
PROTEOMICS 15/16 2019-06-05
2015 Michal Sharon, Amnon Horovitz
Probing allosteric mechanisms using native mass spectrometry
published pages: 7-16, ISSN: 0959-440X, DOI: 10.1016/j.sbi.2015.05.002
Current Opinion in Structural Biology 34 2019-06-05
2017 Hilla Solomon, Bastian Bräuning, Irit Fainer, Gili Ben-Nissan, Stav Rabani, Naomi Goldfinger, Oren Moscovitz, Zippora Shakked, Varda Rotter, Michal Sharon
Post-translational regulation of p53 function through 20S proteasome-mediated cleavage
published pages: 2187-2198, ISSN: 1350-9047, DOI: 10.1038/cdd.2017.139
Cell Death and Differentiation 24/12 2019-06-05
2017 Miri Sokolovski, Jelena Cveticanin, Déborah Hayoun, Ilia Korobko, Michal Sharon, Amnon Horovitz
Measuring inter-protein pairwise interaction energies from a single native mass spectrum by double-mutant cycle analysis
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-017-00285-1
Nature Communications 8/1 2019-06-05
2017 Jinrui Gan, Gili Ben-Nissan, Galina Arkind, Mark Tarnavsky, Devin Trudeau, Lianet Noda Garcia, Dan S. Tawfik, Michal Sharon
Native Mass Spectrometry of Recombinant Proteins from Crude Cell Lysates
published pages: 4398-4404, ISSN: 0003-2700, DOI: 10.1021/acs.analchem.7b00398
Analytical Chemistry 89/8 2019-06-05
2016 Maya A. Olshina, Michal Sharon
Mass spectrometry: a technique of many faces
published pages: , ISSN: 0033-5835, DOI: 10.1017/S0033583516000160
Quarterly Reviews of Biophysics 2019-06-05
2016 Thibault Mayor, Michal Sharon, Michael H. Glickman
Tuning the proteasome to brighten the end of the journey
published pages: , ISSN: 0363-6143, DOI: 10.1152/ajpcell.00198.2016
Cell Physiology 2019-06-05

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