LIGER · Identification of novel substrates for ubiquitin ligases involved in cell cycle and cell migration
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2017-03-01 → 2019-10-09
- EU contribution
- €154,721
- Participants
- 1
- Scheme
- MSCA-IF-EF-RI
Lines connect the coordinator with its partners.
Results in brief
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.
Data: CORDIS, © European Union
Project objective
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.
Original text from CORDIS.
Participants
- USTAV MOLEKULARNI GENETIKY AV CR V.V.I. · Praha 4CoordinatorCzechia
Links
Data: CORDIS, © European Union