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Lamin A/C phosphorylation at serine 22 is a conserved heat shock response to regulate nuclear adaptation during stress
The heat shock (HS) response is crucial for cell survival in harmful environments. Nuclear lamin A/C, encoded by the LMNA gene, contributes towards altered gene expression during HS, but the underlying mechanisms are poorly understood. Here, we show that upon HS, lamin A/C was reversibly phosphoryla...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10022683/ https://www.ncbi.nlm.nih.gov/pubmed/36695453 http://dx.doi.org/10.1242/jcs.259788 |
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author | Virtanen, Laura Holm, Emilia Halme, Mona West, Gun Lindholm, Fanny Gullmets, Josef Irjala, Juho Heliö, Tiina Padzik, Artur Meinander, Annika Eriksson, John E. Taimen, Pekka |
author_facet | Virtanen, Laura Holm, Emilia Halme, Mona West, Gun Lindholm, Fanny Gullmets, Josef Irjala, Juho Heliö, Tiina Padzik, Artur Meinander, Annika Eriksson, John E. Taimen, Pekka |
author_sort | Virtanen, Laura |
collection | PubMed |
description | The heat shock (HS) response is crucial for cell survival in harmful environments. Nuclear lamin A/C, encoded by the LMNA gene, contributes towards altered gene expression during HS, but the underlying mechanisms are poorly understood. Here, we show that upon HS, lamin A/C was reversibly phosphorylated at serine 22 in concert with HSF1 activation in human cells, mouse cells and Drosophila melanogaster in vivo. Consequently, the phosphorylation facilitated nucleoplasmic localization of lamin A/C and nuclear sphericity in response to HS. Interestingly, lamin A/C knock-out cells showed deformed nuclei after HS and were rescued by ectopic expression of wild-type lamin A, but not by a phosphomimetic (S22D) lamin A mutant. Furthermore, HS triggered concurrent downregulation of lamina-associated protein 2α (Lap2α, encoded by TMPO) in wild-type lamin A/C-expressing cells, but a similar response was perturbed in lamin A/C knock-out cells and in LMNA mutant patient fibroblasts, which showed impaired cell cycle arrest under HS and compromised survival at recovery. Taken together, our results suggest that the altered phosphorylation stoichiometry of lamin A/C provides an evolutionarily conserved mechanism to regulate lamina structure and serve nuclear adaptation and cell survival during HS. |
format | Online Article Text |
id | pubmed-10022683 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-100226832023-03-18 Lamin A/C phosphorylation at serine 22 is a conserved heat shock response to regulate nuclear adaptation during stress Virtanen, Laura Holm, Emilia Halme, Mona West, Gun Lindholm, Fanny Gullmets, Josef Irjala, Juho Heliö, Tiina Padzik, Artur Meinander, Annika Eriksson, John E. Taimen, Pekka J Cell Sci Research Article The heat shock (HS) response is crucial for cell survival in harmful environments. Nuclear lamin A/C, encoded by the LMNA gene, contributes towards altered gene expression during HS, but the underlying mechanisms are poorly understood. Here, we show that upon HS, lamin A/C was reversibly phosphorylated at serine 22 in concert with HSF1 activation in human cells, mouse cells and Drosophila melanogaster in vivo. Consequently, the phosphorylation facilitated nucleoplasmic localization of lamin A/C and nuclear sphericity in response to HS. Interestingly, lamin A/C knock-out cells showed deformed nuclei after HS and were rescued by ectopic expression of wild-type lamin A, but not by a phosphomimetic (S22D) lamin A mutant. Furthermore, HS triggered concurrent downregulation of lamina-associated protein 2α (Lap2α, encoded by TMPO) in wild-type lamin A/C-expressing cells, but a similar response was perturbed in lamin A/C knock-out cells and in LMNA mutant patient fibroblasts, which showed impaired cell cycle arrest under HS and compromised survival at recovery. Taken together, our results suggest that the altered phosphorylation stoichiometry of lamin A/C provides an evolutionarily conserved mechanism to regulate lamina structure and serve nuclear adaptation and cell survival during HS. The Company of Biologists Ltd 2023-02-27 /pmc/articles/PMC10022683/ /pubmed/36695453 http://dx.doi.org/10.1242/jcs.259788 Text en © 2023. Published by The Company of Biologists Ltd https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Virtanen, Laura Holm, Emilia Halme, Mona West, Gun Lindholm, Fanny Gullmets, Josef Irjala, Juho Heliö, Tiina Padzik, Artur Meinander, Annika Eriksson, John E. Taimen, Pekka Lamin A/C phosphorylation at serine 22 is a conserved heat shock response to regulate nuclear adaptation during stress |
title | Lamin A/C phosphorylation at serine 22 is a conserved heat shock response to regulate nuclear adaptation during stress |
title_full | Lamin A/C phosphorylation at serine 22 is a conserved heat shock response to regulate nuclear adaptation during stress |
title_fullStr | Lamin A/C phosphorylation at serine 22 is a conserved heat shock response to regulate nuclear adaptation during stress |
title_full_unstemmed | Lamin A/C phosphorylation at serine 22 is a conserved heat shock response to regulate nuclear adaptation during stress |
title_short | Lamin A/C phosphorylation at serine 22 is a conserved heat shock response to regulate nuclear adaptation during stress |
title_sort | lamin a/c phosphorylation at serine 22 is a conserved heat shock response to regulate nuclear adaptation during stress |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10022683/ https://www.ncbi.nlm.nih.gov/pubmed/36695453 http://dx.doi.org/10.1242/jcs.259788 |
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