論文 - 詳細
| RRC ID | 42104 |
|---|---|
| 著者 | Haraguchi T, Holaska JM, Yamane M, Koujin T, Hashiguchi N, Mori C, Wilson KL, Hiraoka Y. |
| タイトル | Emerin binding to Btf, a death-promoting transcriptional repressor, is disrupted by a missense mutation that causes Emery-Dreifuss muscular dystrophy. |
| ジャーナル | Eur J Biochem |
| Abstract |
Loss of functional emerin, a nuclear membrane protein, causes X-linked recessive Emery-Dreifuss muscular dystrophy. In a yeast two-hybrid screen, we found that emerin interacts with Btf, a death-promoting transcriptional repressor, which is expressed at high levels in skeletal muscle. Biochemical analysis showed that emerin binds Btf with an equilibrium affinity (KD) of 100 nm. Using a collection of 21 clustered alanine-substitution mutations in emerin, the residues required for binding to Btf mapped to two regions of emerin that flank its lamin-binding domain. Two disease-causing mutations in emerin, S54F and Delta95-99, disrupted binding to Btf. The Delta95-99 mutation was relatively uninformative, as this mutation also disrupts emerin binding to lamin A and a different transcription repressor named germ cell-less (GCL). In striking contrast, emerin mutant S54F, which binds normally to barrier-to-autointegration factor, lamin A and GCL, selectively disrupted emerin binding to Btf. We localized endogenous Btf in HeLa cells by indirect immunoflurorescence using affinity-purified antibodies against Btf. In nonapoptotic HeLa cells Btf was found in dot-like structures throughout the nuclear interior. However, within 3 h after treating cells with Fas antibody to induce apoptosis, the distribution of Btf changed, and Btf concentrated in a distinct zone near the nuclear envelope. These results suggest that Btf localization is regulated by apoptotic signals, and that loss of emerin binding to Btf may be relevant to muscle wasting in Emery-Dreifuss muscular dystrophy. |
| 巻・号 | 271(5) |
| ページ | 1035-45 |
| 公開日 | 2004-3-1 |
| DOI | 10.1111/j.1432-1033.2004.04007.x |
| PII | 4007 |
| PMID | 15009215 |
| MeSH | Amino Acid Sequence Apoptosis / physiology DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* HeLa Cells Humans Membrane Proteins / genetics* Membrane Proteins / metabolism* Muscular Dystrophy, Emery-Dreifuss / genetics* Muscular Dystrophy, Emery-Dreifuss / metabolism* Mutation, Missense* Nuclear Envelope / metabolism Nuclear Proteins Protein Binding Protein Structure, Tertiary Repressor Proteins / genetics Repressor Proteins / metabolism* Thymopoietins / genetics* Thymopoietins / metabolism* Transcription Factors / genetics Transcription Factors / metabolism* Tumor Suppressor Proteins / genetics Tumor Suppressor Proteins / metabolism* Two-Hybrid System Techniques |
| 引用数 | 111 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| 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 | Wikipedia |
| 各媒体での言及数の合計 | 3 |
| 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 | |
| ヒト・動物細胞 | HeLa(RCB0007) |