Abstract
The endosomal pathway plays a pivotal role upon signal transduction in the Notch pathway. Recent work on lethal (2) giant discs (lgd) points to an additional critical role in avoiding uncontrolled ligand-independent signalling during trafficking of the Notch receptor through the endosomal pathway to the lysosome for degradation. In this chapter, we will outline the journey of Notch through the endosomal system and present an overview of the current knowledge about Lgd and its mammalian orthologs Lgd1/CC2D1b and Lgd2/CC2D1a. We will then discuss how Notch is activated in the absence of lgd function in Drosophila and ask whether there is evidence that a similar ligand-independent activation of the Notch pathway can also happen in mammals if the orthologs are inactivated.
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Acknowledgements
Work in the Klein lab is supported by the Deutsche Forschungsgemeinschaft (DFG) through Teilprojekt B01 of the CRC 1208 “Identity and Dynamics of Membrane Systems-from Molecules to Cellular Functions” and Sachbeihilfe KL-1028/5-2. We apologise to every researcher whose publications are not cited due to restrictions in space. The Reiff lab is supported by the Deutsche Forschungsgemeinschaft (DFG) by Sachbeihilfe RE-3453/3-1 and the Wilhelm Sander-Stiftung 2018.145.1.
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Reiff, T., Baeumers, M., Tibbe, C., Klein, T. (2021). Unravelling of Hidden Secrets: The Tumour Suppressor Lethal (2) Giant Discs (Lgd)/CC2D1, Notch Signalling and Cancer. In: Reichrath, J., Reichrath, S. (eds) Notch Signaling in Embryology and Cancer. Advances in Experimental Medicine and Biology, vol 1287. Springer, Cham. https://doi.org/10.1007/978-3-030-55031-8_3
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