H2020Индивидуална стипендия2017–2019

DUBs26S · Role of a novel proteasome-associated DUB – A boon for therapeutics

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2017-11-01 → 2019-10-31
Финансиране от ЕС: 182 509 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Протеазомите са механизми в клетките, които разграждат повредени протеини, а проектът търси нови ензими (DUBs), които регулират този процес. Разбирането им помага при разработването на лекарства срещу рак и неврологични заболявания, при които работата на протеазомите е нарушена.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

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

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.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

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.

Оригинален текст от CORDIS (на английски).

Участници

TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY · HaifaКоординаторИзраел