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Active nuclear import of the deacetylase Sirtuin-2 is controlled by its C-terminus and importins
The NAD-dependent deacetylase Sirtuin-2 (SIRT2) functions in diverse cellular processes including the cell cycle, metabolism, and has important roles in tumorigenesis and bacterial infection. SIRT2 predominantly resides in the cytoplasm but can also function in the nucleus. Consequently, SIRT2 local...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010746/ https://www.ncbi.nlm.nih.gov/pubmed/32042025 http://dx.doi.org/10.1038/s41598-020-58397-6 |
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author | Eldridge, Matthew J. G. Pereira, Jorge M. Impens, Francis Hamon, Mélanie A. |
author_facet | Eldridge, Matthew J. G. Pereira, Jorge M. Impens, Francis Hamon, Mélanie A. |
author_sort | Eldridge, Matthew J. G. |
collection | PubMed |
description | The NAD-dependent deacetylase Sirtuin-2 (SIRT2) functions in diverse cellular processes including the cell cycle, metabolism, and has important roles in tumorigenesis and bacterial infection. SIRT2 predominantly resides in the cytoplasm but can also function in the nucleus. Consequently, SIRT2 localisation and its interacting partners may greatly impact its function and need to be defined more clearly. In this study we used mass spectrometry to determine the interactomes of SIRT2 in whole cells and in specific cellular fractions; cytoplasm, nucleus and chromatin. Using this approach, we identified novel interacting partners of SIRT2. These included a number of proteins that function in nuclear import. We show that multiple importins interact with and contribute to the basal nuclear shuttling of SIRT2 and that one of these, IPO7 is required for SIRT2 mediated H3K18 deacetylation in response to bacterial infection. Furthermore, we reveal that the unstructured C-terminus of SIRT2 negatively regulates importin-binding and nuclear transport. This study demonstrates that SIRT2 is actively transported into the nucleus via a process regulated by its C-terminus and provides a resource of SIRT2 interacting partners. |
format | Online Article Text |
id | pubmed-7010746 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-70107462020-02-21 Active nuclear import of the deacetylase Sirtuin-2 is controlled by its C-terminus and importins Eldridge, Matthew J. G. Pereira, Jorge M. Impens, Francis Hamon, Mélanie A. Sci Rep Article The NAD-dependent deacetylase Sirtuin-2 (SIRT2) functions in diverse cellular processes including the cell cycle, metabolism, and has important roles in tumorigenesis and bacterial infection. SIRT2 predominantly resides in the cytoplasm but can also function in the nucleus. Consequently, SIRT2 localisation and its interacting partners may greatly impact its function and need to be defined more clearly. In this study we used mass spectrometry to determine the interactomes of SIRT2 in whole cells and in specific cellular fractions; cytoplasm, nucleus and chromatin. Using this approach, we identified novel interacting partners of SIRT2. These included a number of proteins that function in nuclear import. We show that multiple importins interact with and contribute to the basal nuclear shuttling of SIRT2 and that one of these, IPO7 is required for SIRT2 mediated H3K18 deacetylation in response to bacterial infection. Furthermore, we reveal that the unstructured C-terminus of SIRT2 negatively regulates importin-binding and nuclear transport. This study demonstrates that SIRT2 is actively transported into the nucleus via a process regulated by its C-terminus and provides a resource of SIRT2 interacting partners. Nature Publishing Group UK 2020-02-10 /pmc/articles/PMC7010746/ /pubmed/32042025 http://dx.doi.org/10.1038/s41598-020-58397-6 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Eldridge, Matthew J. G. Pereira, Jorge M. Impens, Francis Hamon, Mélanie A. Active nuclear import of the deacetylase Sirtuin-2 is controlled by its C-terminus and importins |
title | Active nuclear import of the deacetylase Sirtuin-2 is controlled by its C-terminus and importins |
title_full | Active nuclear import of the deacetylase Sirtuin-2 is controlled by its C-terminus and importins |
title_fullStr | Active nuclear import of the deacetylase Sirtuin-2 is controlled by its C-terminus and importins |
title_full_unstemmed | Active nuclear import of the deacetylase Sirtuin-2 is controlled by its C-terminus and importins |
title_short | Active nuclear import of the deacetylase Sirtuin-2 is controlled by its C-terminus and importins |
title_sort | active nuclear import of the deacetylase sirtuin-2 is controlled by its c-terminus and importins |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010746/ https://www.ncbi.nlm.nih.gov/pubmed/32042025 http://dx.doi.org/10.1038/s41598-020-58397-6 |
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