PRP-19, a conserved pre-mRNA processing factor and E3 ubiquitin ligase, inhibits the nuclear accumulation of GLP-1/Notch intracellular domain
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 Caenorhabd...
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doaj-a97deb6571094184b91de9c9b335e6e22021-06-02T19:06:49ZengThe Company of BiologistsBiology Open2046-63902018-07-017710.1242/bio.034066034066PRP-19, a conserved pre-mRNA processing factor and E3 ubiquitin ligase, inhibits the nuclear accumulation of GLP-1/Notch intracellular domainSilvia Gutnik0Yann Thomas1Yanwu Guo2Janosch Stoecklin3Anca Neagu4Lionel Pintard5Jorge Merlet6Rafal Ciosk7 Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland Cell Cycle and Development, Institut Jacques Monod, UMR7592 CNRS - Université Paris Diderot, Sorbonne Paris Cité, F-75013 Paris, France Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland Cell Cycle and Development, Institut Jacques Monod, UMR7592 CNRS - Université Paris Diderot, Sorbonne Paris Cité, F-75013 Paris, France Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland 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.http://bio.biologists.org/content/7/7/bio034066Caenorhabditis elegansGLP-1NotchPRP-19SplicingUbiquitin ligase |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Silvia Gutnik Yann Thomas Yanwu Guo Janosch Stoecklin Anca Neagu Lionel Pintard Jorge Merlet Rafal Ciosk |
spellingShingle |
Silvia Gutnik Yann Thomas Yanwu Guo Janosch Stoecklin Anca Neagu Lionel Pintard Jorge Merlet Rafal Ciosk PRP-19, a conserved pre-mRNA processing factor and E3 ubiquitin ligase, inhibits the nuclear accumulation of GLP-1/Notch intracellular domain Biology Open Caenorhabditis elegans GLP-1 Notch PRP-19 Splicing Ubiquitin ligase |
author_facet |
Silvia Gutnik Yann Thomas Yanwu Guo Janosch Stoecklin Anca Neagu Lionel Pintard Jorge Merlet Rafal Ciosk |
author_sort |
Silvia Gutnik |
title |
PRP-19, a conserved pre-mRNA processing factor and E3 ubiquitin ligase, inhibits the nuclear accumulation of GLP-1/Notch intracellular domain |
title_short |
PRP-19, a conserved pre-mRNA processing factor and E3 ubiquitin ligase, inhibits the nuclear accumulation of GLP-1/Notch intracellular domain |
title_full |
PRP-19, a conserved pre-mRNA processing factor and E3 ubiquitin ligase, inhibits the nuclear accumulation of GLP-1/Notch intracellular domain |
title_fullStr |
PRP-19, a conserved pre-mRNA processing factor and E3 ubiquitin ligase, inhibits the nuclear accumulation of GLP-1/Notch intracellular domain |
title_full_unstemmed |
PRP-19, a conserved pre-mRNA processing factor and E3 ubiquitin ligase, inhibits the nuclear accumulation of GLP-1/Notch intracellular domain |
title_sort |
prp-19, a conserved pre-mrna processing factor and e3 ubiquitin ligase, inhibits the nuclear accumulation of glp-1/notch intracellular domain |
publisher |
The Company of Biologists |
series |
Biology Open |
issn |
2046-6390 |
publishDate |
2018-07-01 |
description |
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. |
topic |
Caenorhabditis elegans GLP-1 Notch PRP-19 Splicing Ubiquitin ligase |
url |
http://bio.biologists.org/content/7/7/bio034066 |
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