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

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

Reporting period: 2017-11-01 to 2019-10-31

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.
• 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.
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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