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The anaphase-promoting complex regulates the degradation of the inner nuclear membrane protein Mps3

The nucleus is enclosed by the inner nuclear membrane (INM) and the outer nuclear membrane (ONM). While the ONM is continuous with the endoplasmic reticulum (ER), the INM is independent and separates the nucleoplasm from the ER lumen. Turnover of ER proteins has been well characterized by the ER-ass...

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Autores principales: Koch, Bailey A., Jin, Hui, Tomko, Robert J., Yu, Hong-Guo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400550/
https://www.ncbi.nlm.nih.gov/pubmed/30737264
http://dx.doi.org/10.1083/jcb.201808024
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author Koch, Bailey A.
Jin, Hui
Tomko, Robert J.
Yu, Hong-Guo
author_facet Koch, Bailey A.
Jin, Hui
Tomko, Robert J.
Yu, Hong-Guo
author_sort Koch, Bailey A.
collection PubMed
description The nucleus is enclosed by the inner nuclear membrane (INM) and the outer nuclear membrane (ONM). While the ONM is continuous with the endoplasmic reticulum (ER), the INM is independent and separates the nucleoplasm from the ER lumen. Turnover of ER proteins has been well characterized by the ER-associated protein degradation (ERAD) pathway, but very little is known about turnover of resident INM proteins. Here we show that the anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase, regulates the degradation of Mps3, a conserved integral protein of the INM. Turnover of Mps3 requires the ubiquitin-conjugating enzyme Ubc7, but was independent of the known ERAD ubiquitin ligases Doa10 and Hrd1 as well as the recently discovered Asi1–Asi3 complex. Using a genetic approach, we have found that Cdh1, a coactivator of APC/C, modulates Mps3 stability. APC/C controls Mps3 degradation through Mps3’s N terminus, which resides in the nucleoplasm and possesses two putative APC/C-dependent destruction motifs. Accumulation of Mps3 at the INM impairs nuclear morphological changes and cell division. Our findings therefore reveal an unexpected mechanism of APC/C-mediated protein degradation at the INM that coordinates nuclear morphogenesis and cell cycle progression.
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spelling pubmed-64005502019-09-04 The anaphase-promoting complex regulates the degradation of the inner nuclear membrane protein Mps3 Koch, Bailey A. Jin, Hui Tomko, Robert J. Yu, Hong-Guo J Cell Biol Research Articles The nucleus is enclosed by the inner nuclear membrane (INM) and the outer nuclear membrane (ONM). While the ONM is continuous with the endoplasmic reticulum (ER), the INM is independent and separates the nucleoplasm from the ER lumen. Turnover of ER proteins has been well characterized by the ER-associated protein degradation (ERAD) pathway, but very little is known about turnover of resident INM proteins. Here we show that the anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase, regulates the degradation of Mps3, a conserved integral protein of the INM. Turnover of Mps3 requires the ubiquitin-conjugating enzyme Ubc7, but was independent of the known ERAD ubiquitin ligases Doa10 and Hrd1 as well as the recently discovered Asi1–Asi3 complex. Using a genetic approach, we have found that Cdh1, a coactivator of APC/C, modulates Mps3 stability. APC/C controls Mps3 degradation through Mps3’s N terminus, which resides in the nucleoplasm and possesses two putative APC/C-dependent destruction motifs. Accumulation of Mps3 at the INM impairs nuclear morphological changes and cell division. Our findings therefore reveal an unexpected mechanism of APC/C-mediated protein degradation at the INM that coordinates nuclear morphogenesis and cell cycle progression. Rockefeller University Press 2019-03-04 /pmc/articles/PMC6400550/ /pubmed/30737264 http://dx.doi.org/10.1083/jcb.201808024 Text en © 2019 Koch 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
Koch, Bailey A.
Jin, Hui
Tomko, Robert J.
Yu, Hong-Guo
The anaphase-promoting complex regulates the degradation of the inner nuclear membrane protein Mps3
title The anaphase-promoting complex regulates the degradation of the inner nuclear membrane protein Mps3
title_full The anaphase-promoting complex regulates the degradation of the inner nuclear membrane protein Mps3
title_fullStr The anaphase-promoting complex regulates the degradation of the inner nuclear membrane protein Mps3
title_full_unstemmed The anaphase-promoting complex regulates the degradation of the inner nuclear membrane protein Mps3
title_short The anaphase-promoting complex regulates the degradation of the inner nuclear membrane protein Mps3
title_sort anaphase-promoting complex regulates the degradation of the inner nuclear membrane protein mps3
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400550/
https://www.ncbi.nlm.nih.gov/pubmed/30737264
http://dx.doi.org/10.1083/jcb.201808024
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