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The role of lysines of the intracellular domain of Notch during regulation of the Notch pathway

Subject Area Cell Biology
Term from 2014 to 2019
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 264678793
 
Final Report Year 2021

Final Report Abstract

Our results have clarified the role of K-dependent ubi of the Notch receptor. First of all, they reveal that Notch is endocytosed by several independently operating mechanisms. In addition, they show that ubi is essential for the entry of non-activated constitutive endocytosed Notch molecules into ILVs, a process which separates them from the cytosol and thereby prevents their uncontrolled, ligand-independent 6 activation. Therefore, they also provide an explanation for the uncontrolled activation of the Notch pathway in mutants that regulate the ILV pathway, such as lethal (2) giant disc (lgd) and ESCRT-mutants where Notch is either not included into the intraluminal vesicles or the vesicles are not formed at all. Moreover, the achieved results highlight the consequence and danger of the remaining of Notch in the limiting membrane of endosomes. Therefore, they are of interest for a variety of scientific areas with an interest in cell signalling, ubi, endocytosis and also cancer biology.

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