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

Informations projet

DUBs26S

N° de convention de subvention: 748804

DOI

10.3030/748804

Projet clôturé

Date de signature de la CE 6 Avril 2017

Date de début 1 Novembre 2017

Date de fin 31 Octobre 2019

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 182 509,20

Contribution de l’UE

€ 182 509,20

Coordonné par

TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY
Israel

Periodic Reporting for period 1 - DUBs26S (Role of a novel proteasome-associated DUB – A boon for therapeutics)

Période du rapport: 2017-11-01 au 2019-10-31

Résumé du contexte et des objectifs généraux du projet

The problem/issue being addressed:
Proteasome-complex is a protein degradation machinery which degrades damaged, unused and miss-folded proteins in eukaryotic cells. This process is aided by many enzymes at proteasomes of two types; integral subunits and associated subunits. Among the associated subunits “Deubiquitinase Enzymes (DUBs)” are the major modulators. Only very few of them are characterized yet not subjectively studied and many more are still to be discovered. The current study has addressed the question for the possibility of more DUBs on proteasomes although spatio-temporal manner but effective enough to modulate proteasome function significantly.

Why is it important for society?
The proteasome associated DUBs are good target for drug development because (1) they are enzymes, and (2) their interaction to proteasome may be disease specific. Modulating their activity will be resulted in resuming proteasome’s function to normal and consequently can combat the disease. Many diseases like Cancer and Neurodisorders shows defects in proteasome functions and increasing research reports suggest the involvement of these proteasome associated proteins. So understanding the basic role of these proteins on proteasomes will forge ideas to manipulate them for disease clearance. And finally will benefit the overall health status and life-style of the society.

The overall objectives are:
1- To understand proteasome function under different disease conditions.
2- To define the determinants and regulation of proteasome function.
3- To evaluate the possibility of new DUBs interaction with proteasomes.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

• Developing and improving methods for Proteasome purification from different mammalian sources.
• Purifying different population of proteasomes (20S & 26S) for detailed proteolytic studies.
• Molecular cloning of some DUBs (USP9X and USP14) along with their separate domains for bacterial expression.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

Currently the role of proteasome associated DUBs is a hot research topic globally. Until now a handful number of DUBs were characterized as proteasome regulators and even very few are well studied for their role. The study expect more proteasome associated DUBs and their role in proteasome modulation for protein degradation.
Apart from the DUBs other determinants which fine tune the protein degradation process at proteasome were also the interest of the current research.

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