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Importin-β negatively regulates multiple aspects of mitosis including RANGAP1 recruitment to kinetochores
Importin-β is the main vector for interphase nuclear protein import and plays roles after nuclear envelope breakdown. Here we show that importin-β regulates multiple aspects of mitosis via distinct domains that interact with different classes of proteins in human cells. The C-terminal region (which...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3283988/ https://www.ncbi.nlm.nih.gov/pubmed/22331847 http://dx.doi.org/10.1083/jcb.201109104 |
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author | Roscioli, Emanuele Di Francesco, Laura Bolognesi, Alessio Giubettini, Maria Orlando, Serena Harel, Amnon Schininà, Maria Eugenia Lavia, Patrizia |
author_facet | Roscioli, Emanuele Di Francesco, Laura Bolognesi, Alessio Giubettini, Maria Orlando, Serena Harel, Amnon Schininà, Maria Eugenia Lavia, Patrizia |
author_sort | Roscioli, Emanuele |
collection | PubMed |
description | Importin-β is the main vector for interphase nuclear protein import and plays roles after nuclear envelope breakdown. Here we show that importin-β regulates multiple aspects of mitosis via distinct domains that interact with different classes of proteins in human cells. The C-terminal region (which binds importin-α) inhibits mitotic spindle pole formation. The central region (harboring nucleoporin-binding sites) regulates microtubule dynamic functions and interaction with kinetochores. Importin-β interacts through this region with NUP358/RANBP2, which in turn binds SUMO-conjugated RANGAP1 in nuclear pores. We show that this interaction continues after nuclear pore disassembly. Overexpression of importin-β, or of the nucleoporin-binding region, inhibited RANGAP1 recruitment to mitotic kinetochores, an event that is known to require microtubule attachment and the exportin CRM1. Co-expressing either importin-β–interacting RANBP2 fragments, or CRM1, restored RANGAP1 to kinetochores and rescued importin-β–dependent mitotic dynamic defects. These results reveal previously unrecognized importin-β functions at kinetochores exerted via RANBP2 and opposed by CRM1. |
format | Online Article Text |
id | pubmed-3283988 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-32839882012-08-20 Importin-β negatively regulates multiple aspects of mitosis including RANGAP1 recruitment to kinetochores Roscioli, Emanuele Di Francesco, Laura Bolognesi, Alessio Giubettini, Maria Orlando, Serena Harel, Amnon Schininà, Maria Eugenia Lavia, Patrizia J Cell Biol Research Articles Importin-β is the main vector for interphase nuclear protein import and plays roles after nuclear envelope breakdown. Here we show that importin-β regulates multiple aspects of mitosis via distinct domains that interact with different classes of proteins in human cells. The C-terminal region (which binds importin-α) inhibits mitotic spindle pole formation. The central region (harboring nucleoporin-binding sites) regulates microtubule dynamic functions and interaction with kinetochores. Importin-β interacts through this region with NUP358/RANBP2, which in turn binds SUMO-conjugated RANGAP1 in nuclear pores. We show that this interaction continues after nuclear pore disassembly. Overexpression of importin-β, or of the nucleoporin-binding region, inhibited RANGAP1 recruitment to mitotic kinetochores, an event that is known to require microtubule attachment and the exportin CRM1. Co-expressing either importin-β–interacting RANBP2 fragments, or CRM1, restored RANGAP1 to kinetochores and rescued importin-β–dependent mitotic dynamic defects. These results reveal previously unrecognized importin-β functions at kinetochores exerted via RANBP2 and opposed by CRM1. The Rockefeller University Press 2012-02-20 /pmc/articles/PMC3283988/ /pubmed/22331847 http://dx.doi.org/10.1083/jcb.201109104 Text en © 2012 Roscioli et al. 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 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Roscioli, Emanuele Di Francesco, Laura Bolognesi, Alessio Giubettini, Maria Orlando, Serena Harel, Amnon Schininà, Maria Eugenia Lavia, Patrizia Importin-β negatively regulates multiple aspects of mitosis including RANGAP1 recruitment to kinetochores |
title | Importin-β negatively regulates multiple aspects of mitosis including RANGAP1 recruitment to kinetochores |
title_full | Importin-β negatively regulates multiple aspects of mitosis including RANGAP1 recruitment to kinetochores |
title_fullStr | Importin-β negatively regulates multiple aspects of mitosis including RANGAP1 recruitment to kinetochores |
title_full_unstemmed | Importin-β negatively regulates multiple aspects of mitosis including RANGAP1 recruitment to kinetochores |
title_short | Importin-β negatively regulates multiple aspects of mitosis including RANGAP1 recruitment to kinetochores |
title_sort | importin-β negatively regulates multiple aspects of mitosis including rangap1 recruitment to kinetochores |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3283988/ https://www.ncbi.nlm.nih.gov/pubmed/22331847 http://dx.doi.org/10.1083/jcb.201109104 |
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