Catenin-Condensation · The effect of β-catenin condensation on the Wnt-pathway
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2020-04-01 → 2022-03-31
- Финансиране от ЕС
- 187 572 €
- Участници
- 1
- Схема
- MSCA-IF-EF-RI
Линиите свързват координатора с партньорите.
Накратко на български
Белтъкът $\beta$-catenin образува капки в ядрото на клетката, като се изследва как това влияе върху комуникацията между клетките. По-доброто разбиране на този процес помага при изучаването на развитието на ембриона, регенерацията на тъкани и рака.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
The effect of β-catenin condensation on the Wnt-pathway
Specialized signaling pathways allow communication between cells in the body and mis-regulation of these pathways almost invariably leads to disease. β-catenin is a key signal-transduction protein in the highly conserved Wnt-signalling pathway, regulating cell fate specification, proliferation and differentiation during development and in various adult tissues. Errors in the Wnt-pathway lead to severe developmental disorders in the embryo and cancer in the gut, breast or blood in adults. To achieve its role, β-catenin is present at the plasma membrane, in the cytoplasm and in the cell nucleus. In all these distinct sites β-catenin needs to be highly localized and organized. How this organization takes place is currently unknown. We have recently found that β-catenin can condensate into protein droplets together with other key proteins in the nucleus. In this work we aim to uncover how the condensation of β-catenin into protein droplets impacts the Wnt signalling pathway at the membrane and in the cytoplasm. Deeper knowledge of the fundamental Wnt signalling pathway can have a profound impact on the understanding of embryonic development, adult regeneration and cancer.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
The Wnt-signaling pathway is a key determinant of cell identity and proliferation. However, when aberrantly activated it drives malignant cell proliferation in gastrointestinal cancer, breast cancer, melanoma and leukemia. The key effector protein of the Wnt pathway is β-catenin, which is continuously degraded in unstimulated cells, but in stimulated cells it accumulates and translocates to the nucleus where it activates transcription. A growing body of literature indicates that transcription factors and co-activators interact through the formation of biomolecular condensates. These are membraneless organelles that concentrate and compartmentalise components through weak, but multivalent interactions. Recently, I have shown that β-catenin forms condensates with Mediator co-activator to specifically activate transcription. However, how this new mode of β-catenin interactions influences the rest of the Wnt-pathway is currently unknown. The overarching goal of this proposal is to uncover how β-catenin condensation impacts the Wnt-signaling pathway. I will investigate the consequences of β-catenin condensation for its cytoplasmic regulation by the destruction complex, study how it affects β-catenin co-factor interactions in the nucleus and determine the effect of oncogenic Wnt-signaling on β-catenin condensates. The proposed work will uncover if β-catenin condensation has a function in the Wnt-signaling pathway outside the nucleus, its effect on co-factor interactions and elucidate how it might contribute to cancer etiology. Deeper understanding of the fundamental Wnt-signaling pathway will have a profound impact on our comprehension of embryonic development, adult regeneration and cancer.
Оригинален текст от CORDIS (на английски).
Участници
- UNIVERSITAIR MEDISCH CENTRUM UTRECHT · UtrechtКоординаторНидерландия
Връзки
Данни: CORDIS, © Европейски съюз