Abstract |
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.
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Authors | Dan N Simon, Tera Domaradzki, Wilma A Hofmann, Katherine L Wilson |
Journal | Molecular biology of the cell
(Mol Biol Cell)
Vol. 24
Issue 3
Pg. 342-50
(Feb 2013)
ISSN: 1939-4586 [Electronic] United States |
PMID | 23243001
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- LMNA protein, human
- Lamin Type A
- SUMO-1 Protein
- SUMO1 protein, human
- SUMO2 protein, human
- Small Ubiquitin-Related Modifier Proteins
- Ubiquitin-Protein Ligase Complexes
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Topics |
- Amino Acid Motifs
- Animals
- COS Cells
- Chlorocebus aethiops
- HeLa Cells
- Humans
- Lamin Type A
(chemistry, genetics)
- Lipodystrophy, Familial Partial
(genetics)
- Mutation, Missense
- SUMO-1 Protein
(chemistry, metabolism)
- Small Ubiquitin-Related Modifier Proteins
(chemistry, metabolism)
- Sumoylation
- Ubiquitin-Protein Ligase Complexes
(chemistry, metabolism)
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