H2020Индивидуална стипендия2017–2019

LIGER · Identification of novel substrates for ubiquitin ligases involved in cell cycle and cell migration

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

Период: 2017-03-01 → 2019-10-09
Финансиране от ЕС: 154 721 €
Участници: 1
Схема: MSCA-IF-EF-RI

Линиите свързват координатора с партньорите.

Накратко на български

Ензимите, наречени E3-убиквитин лигази, разпознават и насочват специфични протеини към разграждане, за да се поддържа балансът в клетката. Разбирането на тези механизми помага при изучаването на патологични състояния като рака и нарушенията в развитието.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Identification of novel substrates for ubiquitin ligases involved in cell cycle and cell migration

Protein degradation via the proteasome-ubiquitin system (UPS) plays a crucial role in cellular homeostasis. Defects in this system are often associated with pathologic states like cancer or developmental abnormalities. E3-ubiquitin ligases are responsible for substrate recognition and subsequent degradation. Despite this fact, many of the ubiquitin ligases have not been paired with any specific substrate yet. In my project supported by MSCA, I focused on “orphan” ubiquitin ligases with unknown functions and substrates. The objectives of the project were based on systematic and functional analysis of these ubiquitin ligases. I aspire to select several of them potentially involved in processes underlying above mentioned pathological states. The main motto and relevance of this approach were centered on the idea that novel biological therapies in the future will require a deep understanding of cellular mechanisms required for cellular growth and survival and that only basic research and detailed biochemical analysis could provide these facts.

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

Цел на проекта

Cancer cells heavily rely on the proteasome-ubiquitin system mediated tuning of proteins stability and proteome composition. Proteasome and ubiquitin ligases targeting drugs are already in use against certain haematological cancers, and similar inhibitors are currently explored as a possibility for autoimmune diseases and parasite infestation treatment. E3 ubiquitin ligases are the ultimate target for these therapies as they determine specificity in substrate recognition. It is thus of utmost interest for both basic and translational research to find new ubiquitin ligases essential for cell proliferation, cell migration or cancer progression and couple them with their substrates. In the proposed LIGER project, we aspire to fuse cutting-edge methods to identify new ubiquitin ligase – substrate pairs. In particular, we will focus on E3 ubiquitin ligases involved in cancer progression and more specifically, in its two crucial aspects - cell growth and cell migration. To pre-select the ubiquitin ligases for further analysis, we will perform an unbiased screen for ubiquitin ligases that are involved in cell growth and cell migration. To achieve this goal, CRISPR library screening methodology will be employed. Consequentially, we will purify proteins associated with the selected ubiquitin ligases and identify their potential substrates. Standard biochemical and molecular biology methods will allow us to study in detail the protein interface between the ubiquitin ligases and their novel substrates and describe the biological function of their degradation. LIGER project will increase our understanding of ubiquitin pathway in physiological and pathological conditions and identify new potential targets for cancer therapy.

Оригинален текст от CORDIS (на английски).

Участници

USTAV MOLEKULARNI GENETIKY AV CR V.V.I. · Praha 4КоординаторЧехия