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Coӧrdinatie van de celcyclus en DNA-foutenherstel via de eiwitfosfatase-1-regulator NIPP1.
NIPP1 is an inhibitor of protein phosphatase-1 (PP1) and controls key signaling pathways of cell proliferation, DNA-damage signalling and oncogenesis. With this research project we propose to explore the molecular basis of NIPP1 functions. Using newly developed mouse models and cell-based tools we will examine whether the established NIPP1 functions are all mediated by associated PP1. We will also investigate whether NIPP1 is a DNA-damage checkpoint component that can be inactivated to induce a cell-cycle arrest and promote DNA repair via a newly identified signaling complex that is scaffolded by protein kinase ATM. Finally, we will examine whether the insensitivity of NIPP1-depleted tissues and cultured cells to mutagens is explained by an enhanced ATM-controlled DNA-repair capacity, senescence of tumor-forming stem cells, and/or an adaptive immune response. This basic research project will generate mechanistic insights that can possibly be exploited for the design of novel therapies that target key oncogenic signaling pathways.
Datum:1 mrt 2021 → Heden
Trefwoorden:NIPP1, DNA Damage, Cell cycle
Project type:PhD project