PRP-19, a conserved pre-mRNA processing factor and E3 ubiquitin ligase, inhibits the nuclear accumulation of GLP-1/Notch intracellular domain
| Autor: | Jorge Merlet, Yanwu Guo, Silvia Gutnik, Yann Thomas, Rafal Ciosk, Janosch Stoecklin, Lionel Pintard, Anca Neagu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Notch QH301-705.5 Science Notch signaling pathway Splicing General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Splicing factor Ubiquitin PRP-19 medicine Biology (General) Caenorhabditis elegans biology biology.organism_classification 3. Good health Ubiquitin ligase Cell biology 030104 developmental biology medicine.anatomical_structure RNA splicing biology.protein Stem cell General Agricultural and Biological Sciences GLP-1 Germ cell Research Article |
| Zdroj: | Biology Open Biology Open, Vol 7, Iss 7 (2018) |
| ISSN: | 2046-6390 |
| Popis: | 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. Summary: GFP tagging of endogenous GLP-1/Notch revealed life stage-specific differences in the nuclear accumulation of GLP-1 intracellular domain, which are mediated by the ubiquitin-proteolytic system and the splicing factor/E3 ubiquitin ligase PRP-19. |
| Databáze: | OpenAIRE |
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