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Ubiquitination of the PI3-kinase VPS-34 promotes VPS-34 stability and phagosome maturation
Apoptotic cells generated by programmed cell death are engulfed by phagocytes and enclosed within membrane-bound phagosomes. Maturation of apoptotic cell–containing phagosomes leads to formation of phagolysosomes where cell corpses are degraded. The class III phosphatidylinositol 3-kinase (PI3-kinas...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748982/ https://www.ncbi.nlm.nih.gov/pubmed/29092895 http://dx.doi.org/10.1083/jcb.201705116 |
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author | Liu, Jinchao Li, Meijiao Li, Lin Chen, She Wang, Xiaochen |
author_facet | Liu, Jinchao Li, Meijiao Li, Lin Chen, She Wang, Xiaochen |
author_sort | Liu, Jinchao |
collection | PubMed |
description | Apoptotic cells generated by programmed cell death are engulfed by phagocytes and enclosed within membrane-bound phagosomes. Maturation of apoptotic cell–containing phagosomes leads to formation of phagolysosomes where cell corpses are degraded. The class III phosphatidylinositol 3-kinase (PI3-kinase) VPS-34 coordinates with PIKI-1, a class II PI3-kinase, to produce PtdIns3P on phagosomes, thus promoting phagosome closure and maturation. Here, we identified UBC-13, an E2 ubiquitin–conjugating enzyme that functions in the same pathway with VPS-34 but in parallel to PIKI-1 to regulate PtdIns3P generation on phagosomes. Loss of ubc-13 affects early steps of phagosome maturation, causing accumulation of cell corpses. We found that UBC-13 functions with UEV-1, a noncatalytic E2 variant, and CHN-1, a U-box–containing E3 ubiquitin ligase, to catalyze K63-linked poly-ubiquitination on VPS-34 both in vitro and in Caenorhabditis elegans. Loss of ubc-13, uev-1, or chn-1 disrupts ubiquitin modification of VPS-34 and causes significantly reduced VPS-34 protein levels. Our data suggest that K63-linked ubiquitin modification serves as a general mechanism to modulate VPS-34 stability in multiple processes. |
format | Online Article Text |
id | pubmed-5748982 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-57489822018-07-02 Ubiquitination of the PI3-kinase VPS-34 promotes VPS-34 stability and phagosome maturation Liu, Jinchao Li, Meijiao Li, Lin Chen, She Wang, Xiaochen J Cell Biol Research Articles Apoptotic cells generated by programmed cell death are engulfed by phagocytes and enclosed within membrane-bound phagosomes. Maturation of apoptotic cell–containing phagosomes leads to formation of phagolysosomes where cell corpses are degraded. The class III phosphatidylinositol 3-kinase (PI3-kinase) VPS-34 coordinates with PIKI-1, a class II PI3-kinase, to produce PtdIns3P on phagosomes, thus promoting phagosome closure and maturation. Here, we identified UBC-13, an E2 ubiquitin–conjugating enzyme that functions in the same pathway with VPS-34 but in parallel to PIKI-1 to regulate PtdIns3P generation on phagosomes. Loss of ubc-13 affects early steps of phagosome maturation, causing accumulation of cell corpses. We found that UBC-13 functions with UEV-1, a noncatalytic E2 variant, and CHN-1, a U-box–containing E3 ubiquitin ligase, to catalyze K63-linked poly-ubiquitination on VPS-34 both in vitro and in Caenorhabditis elegans. Loss of ubc-13, uev-1, or chn-1 disrupts ubiquitin modification of VPS-34 and causes significantly reduced VPS-34 protein levels. Our data suggest that K63-linked ubiquitin modification serves as a general mechanism to modulate VPS-34 stability in multiple processes. The Rockefeller University Press 2018-01-02 /pmc/articles/PMC5748982/ /pubmed/29092895 http://dx.doi.org/10.1083/jcb.201705116 Text en © 2018 Liu et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Liu, Jinchao Li, Meijiao Li, Lin Chen, She Wang, Xiaochen Ubiquitination of the PI3-kinase VPS-34 promotes VPS-34 stability and phagosome maturation |
title | Ubiquitination of the PI3-kinase VPS-34 promotes VPS-34 stability and phagosome maturation |
title_full | Ubiquitination of the PI3-kinase VPS-34 promotes VPS-34 stability and phagosome maturation |
title_fullStr | Ubiquitination of the PI3-kinase VPS-34 promotes VPS-34 stability and phagosome maturation |
title_full_unstemmed | Ubiquitination of the PI3-kinase VPS-34 promotes VPS-34 stability and phagosome maturation |
title_short | Ubiquitination of the PI3-kinase VPS-34 promotes VPS-34 stability and phagosome maturation |
title_sort | ubiquitination of the pi3-kinase vps-34 promotes vps-34 stability and phagosome maturation |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748982/ https://www.ncbi.nlm.nih.gov/pubmed/29092895 http://dx.doi.org/10.1083/jcb.201705116 |
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