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Lamin A tail modification by SUMO1 is disrupted by familial partial lipodystrophy–causing mutations
Lamin filaments are major components of the nucleoskeleton that bind LINC complexes and many nuclear membrane proteins. The tail domain of lamin A directly binds 21 known partners, including actin, emerin, and SREBP1, but how these interactions are regulated is unknown. We report small ubiquitin-lik...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564541/ https://www.ncbi.nlm.nih.gov/pubmed/23243001 http://dx.doi.org/10.1091/mbc.E12-07-0527 |
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author | Simon, Dan N. Domaradzki, Tera Hofmann, Wilma A. Wilson, Katherine L. |
author_facet | Simon, Dan N. Domaradzki, Tera Hofmann, Wilma A. Wilson, Katherine L. |
author_sort | Simon, Dan N. |
collection | PubMed |
description | Lamin filaments are major components of the nucleoskeleton that bind LINC complexes and many nuclear membrane proteins. The tail domain of lamin A directly binds 21 known partners, including actin, emerin, and SREBP1, but how these interactions are regulated is unknown. We report small ubiquitin-like modifier 1 (SUMO1) as a major new posttranslational modification of the lamin A tail. Two SUMO1 modification sites were identified based on in vitro SUMOylation assays and studies of Cos-7 cells. One site (K420) matches the SUMO1 target consensus; the other (K486) does not. On the basis of the position of K486 on the lamin A Ig-fold, we hypothesize the SUMO1 E2 enzyme recognizes a folded structure–dependent motif that includes residues genetically linked to familial partial lipodystrophy (FPLD). Supporting this model, SUMO1-modification of the lamin A tail is reduced by two FPLD-causing mutations, G465D and K486N, and by single mutations in acidic residues E460 and D461. These results suggest a novel mode of functional control over lamin A in cells. |
format | Online Article Text |
id | pubmed-3564541 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-35645412013-04-16 Lamin A tail modification by SUMO1 is disrupted by familial partial lipodystrophy–causing mutations Simon, Dan N. Domaradzki, Tera Hofmann, Wilma A. Wilson, Katherine L. Mol Biol Cell Articles Lamin filaments are major components of the nucleoskeleton that bind LINC complexes and many nuclear membrane proteins. The tail domain of lamin A directly binds 21 known partners, including actin, emerin, and SREBP1, but how these interactions are regulated is unknown. We report small ubiquitin-like modifier 1 (SUMO1) as a major new posttranslational modification of the lamin A tail. Two SUMO1 modification sites were identified based on in vitro SUMOylation assays and studies of Cos-7 cells. One site (K420) matches the SUMO1 target consensus; the other (K486) does not. On the basis of the position of K486 on the lamin A Ig-fold, we hypothesize the SUMO1 E2 enzyme recognizes a folded structure–dependent motif that includes residues genetically linked to familial partial lipodystrophy (FPLD). Supporting this model, SUMO1-modification of the lamin A tail is reduced by two FPLD-causing mutations, G465D and K486N, and by single mutations in acidic residues E460 and D461. These results suggest a novel mode of functional control over lamin A in cells. The American Society for Cell Biology 2013-02-01 /pmc/articles/PMC3564541/ /pubmed/23243001 http://dx.doi.org/10.1091/mbc.E12-07-0527 Text en © 2013 Simon et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Simon, Dan N. Domaradzki, Tera Hofmann, Wilma A. Wilson, Katherine L. Lamin A tail modification by SUMO1 is disrupted by familial partial lipodystrophy–causing mutations |
title | Lamin A tail modification by SUMO1 is disrupted by familial partial lipodystrophy–causing mutations |
title_full | Lamin A tail modification by SUMO1 is disrupted by familial partial lipodystrophy–causing mutations |
title_fullStr | Lamin A tail modification by SUMO1 is disrupted by familial partial lipodystrophy–causing mutations |
title_full_unstemmed | Lamin A tail modification by SUMO1 is disrupted by familial partial lipodystrophy–causing mutations |
title_short | Lamin A tail modification by SUMO1 is disrupted by familial partial lipodystrophy–causing mutations |
title_sort | lamin a tail modification by sumo1 is disrupted by familial partial lipodystrophy–causing mutations |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564541/ https://www.ncbi.nlm.nih.gov/pubmed/23243001 http://dx.doi.org/10.1091/mbc.E12-07-0527 |
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