論文 - 詳細
| RRC ID | 67655 |
|---|---|
| 著者 | Moriuchi T, Muraoka T, Mio K, Osumi T, Hirose F. |
| タイトル | Long-term expression of the lamin A mutant associated with dilated cardiomyopathy induces senescence. |
| ジャーナル | Genes Cells |
| Abstract |
Mutation of the lamin A gene (LMNA) causes a diverse range of diseases referred to as laminopathies. Because most laminopathies have a dominant inheritance pattern and progress gradually, cultured cells stably expressing mutant lamin A at the same level as endogenous wild-type cells are required for chronological analysis. In this study, we showed that an expression system involving a lentiviral vector that carries the human metallothionein gene basal promoter ensures stable and basal-level expression of proteins and is thus suitable for investigating the properties of lamin A mutants. The small ubiquitin-related modifier (SUMO) modification (SUMOylation)-defective E203G mutant that is associated with familial dilated cardiomyopathy exhibited abnormal subnuclear distribution and inhibited normal localization of WT lamin A in a dominant-negative manner. Low-level and long-term expression of the E203G mutant resulted in multinucleated giant cells, aberrant lipid droplet accumulation in the cytoplasm and premature senescence. Expression of another SUMOylation-defective mutant (K201R) did not induce any phenotypes observed in cells expressing E203G. These results indicate that the E203G mutant may inhibit the normal functions of wild-type lamin A in a dominant-negative manner, but a defect in SUMOylation itself may not be involved in disease pathogenesis. |
| 巻・号 | 19(12) |
| ページ | 901-18 |
| 公開日 | 2014-12-1 |
| DOI | 10.1111/gtc.12189 |
| PMID | 25319090 |
| MeSH | Cardiomyopathy, Dilated / metabolism Cardiomyopathy, Dilated / pathology* Cell Nucleus / metabolism Cell Proliferation Cellular Senescence Giant Cells / metabolism Giant Cells / pathology HEK293 Cells HeLa Cells Heterochromatin / metabolism Humans Lamin Type A / metabolism* Lamin Type B / metabolism Lipid Metabolism Mutation Sumoylation |
| IF | 1.655 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393) |