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Biol Open. 2018 Jul 16;7(7). pii: bio034066. doi: 10.1242/bio.034066.

PRP-19, a conserved pre-mRNA processing factor and E3 ubiquitin ligase, inhibits the nuclear accumulation of GLP-1/Notch intracellular domain.

Author information

1
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
2
University of Basel, Petersplatz 1, 4001 Basel, Switzerland.
3
Cell Cycle and Development, Institut Jacques Monod, UMR7592 CNRS - Université Paris Diderot, Sorbonne Paris Cité, F-75013 Paris, France.
4
Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, 0316 Oslo, Norway.
5
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland jorge.merlet@sorbonne-universite.fr rafal.ciosk@ibv.uio.no rafal.ciosk@ibch.poznan.pl.
6
Sorbonne Université, CNRS, Institut de Biologie Paris-Seine (IBPS), Developmental Biology Laboratory, UMR 7622, F-75005 Paris, France.
7
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland.

Abstract

The Notch signalling pathway is a conserved and widespread signalling paradigm, and its misregulation has been implicated in numerous disorders, including cancer. The output of Notch signalling depends on the nuclear accumulation of the Notch receptor intracellular domain (ICD). Using the Caenorhabditis elegans germline, where GLP-1/Notch-mediated signalling is essential for maintaining stem cells, we monitored GLP-1 in vivo We found that the nuclear enrichment of GLP-1 ICD is dynamic: while the ICD is enriched in germ cell nuclei during larval development, it is depleted from the nuclei in adult germlines. We found that this pattern depends on the ubiquitin proteolytic system and the splicing machinery and, identified the splicing factor PRP-19 as a candidate E3 ubiquitin ligase required for the nuclear depletion of GLP-1 ICD.

KEYWORDS:

Caenorhabditis elegans; GLP-1; Notch; PRP-19; Splicing; Ubiquitin ligase

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