Stress-induced release of Oct-1 from the nuclear envelope is mediated by JNK phosphorylation of lamin B1.
The nuclear lamina can bind and sequester transcription factors (TFs), a function lost if the lamina is abnormal, with missing or mutant lamin proteins. We now show that TF sequestration is not all-or-nothing, but a dynamic physiological response to external signals. We show that the binding of the...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0177990&type=printable |
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| author | Ivan I Boubriak Ashraf N Malhas Marek M Drozdz Lior Pytowski David J Vaux |
| author_facet | Ivan I Boubriak Ashraf N Malhas Marek M Drozdz Lior Pytowski David J Vaux |
| author_sort | Ivan I Boubriak |
| collection | DOAJ |
| description | The nuclear lamina can bind and sequester transcription factors (TFs), a function lost if the lamina is abnormal, with missing or mutant lamin proteins. We now show that TF sequestration is not all-or-nothing, but a dynamic physiological response to external signals. We show that the binding of the ubiquitous TF, Oct-1, to lamin B1 was reversed under conditions of cellular stress caused, inter alia, by the chemical methylating agent methylmethanesulfonate (MMS). A search for lamin B1 post-translational modifications that might mediate changes in Oct-1 binding using kinase inhibitors uncovered a role for c-Jun N-terminal kinase (JNK). Phosphoproteomic and site-directed mutagenesis analyses of lamin B1 isolated from control and MMS-treated nuclei identified T575 as a JNK site phosphorylated after stress. A new phospho-T575 specific anti-peptide antibody confirmed increased interphase cellular T575 phosphorylation after cell exposure to certain stress conditions, enabling us to conclude that lamin B1 acts as an interphase kinase target, releasing Oct-1 to execute a protective response to stress. |
| format | Article |
| id | doaj-art-9b6767ceb5ab4ceb8cf96ef97f658859 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-9b6767ceb5ab4ceb8cf96ef97f6588592025-08-20T02:31:59ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01125e017799010.1371/journal.pone.0177990Stress-induced release of Oct-1 from the nuclear envelope is mediated by JNK phosphorylation of lamin B1.Ivan I BoubriakAshraf N MalhasMarek M DrozdzLior PytowskiDavid J VauxThe nuclear lamina can bind and sequester transcription factors (TFs), a function lost if the lamina is abnormal, with missing or mutant lamin proteins. We now show that TF sequestration is not all-or-nothing, but a dynamic physiological response to external signals. We show that the binding of the ubiquitous TF, Oct-1, to lamin B1 was reversed under conditions of cellular stress caused, inter alia, by the chemical methylating agent methylmethanesulfonate (MMS). A search for lamin B1 post-translational modifications that might mediate changes in Oct-1 binding using kinase inhibitors uncovered a role for c-Jun N-terminal kinase (JNK). Phosphoproteomic and site-directed mutagenesis analyses of lamin B1 isolated from control and MMS-treated nuclei identified T575 as a JNK site phosphorylated after stress. A new phospho-T575 specific anti-peptide antibody confirmed increased interphase cellular T575 phosphorylation after cell exposure to certain stress conditions, enabling us to conclude that lamin B1 acts as an interphase kinase target, releasing Oct-1 to execute a protective response to stress.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0177990&type=printable |
| spellingShingle | Ivan I Boubriak Ashraf N Malhas Marek M Drozdz Lior Pytowski David J Vaux Stress-induced release of Oct-1 from the nuclear envelope is mediated by JNK phosphorylation of lamin B1. PLoS ONE |
| title | Stress-induced release of Oct-1 from the nuclear envelope is mediated by JNK phosphorylation of lamin B1. |
| title_full | Stress-induced release of Oct-1 from the nuclear envelope is mediated by JNK phosphorylation of lamin B1. |
| title_fullStr | Stress-induced release of Oct-1 from the nuclear envelope is mediated by JNK phosphorylation of lamin B1. |
| title_full_unstemmed | Stress-induced release of Oct-1 from the nuclear envelope is mediated by JNK phosphorylation of lamin B1. |
| title_short | Stress-induced release of Oct-1 from the nuclear envelope is mediated by JNK phosphorylation of lamin B1. |
| title_sort | stress induced release of oct 1 from the nuclear envelope is mediated by jnk phosphorylation of lamin b1 |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0177990&type=printable |
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