論文 - 詳細
| RRC ID | 45624 |
|---|---|
| 著者 | Periz G, Lu J, Zhang T, Kankel MW, Jablonski AM, Kalb R, McCampbell A, Wang J. |
| タイトル | Regulation of protein quality control by UBE4B and LSD1 through p53-mediated transcription. |
| ジャーナル | PLoS Biol |
| Abstract |
Protein quality control is essential for clearing misfolded and aggregated proteins from the cell, and its failure is associated with many neurodegenerative disorders. Here, we identify two genes, ufd-2 and spr-5, that when inactivated, synergistically and robustly suppress neurotoxicity associated with misfolded proteins in Caenorhabditis elegans. Loss of human orthologs ubiquitination factor E4 B (UBE4B) and lysine-specific demethylase 1 (LSD1), respectively encoding a ubiquitin ligase and a lysine-specific demethylase, promotes the clearance of misfolded proteins in mammalian cells by activating both proteasomal and autophagic degradation machineries. An unbiased search in this pathway reveals a downstream effector as the transcription factor p53, a shared substrate of UBE4B and LSD1 that functions as a key regulator of protein quality control to protect against proteotoxicity. These studies identify a new protein quality control pathway via regulation of transcription factors and point to the augmentation of protein quality control as a wide-spectrum antiproteotoxicity strategy. |
| 巻・号 | 13(4) |
| ページ | e1002114 |
| 公開日 | 2015-4-1 |
| DOI | 10.1371/journal.pbio.1002114 |
| PII | PBIOLOGY-D-14-04412 |
| PMID | 25837623 |
| PMC | PMC4383508 |
| MeSH | Animals Autophagy Caenorhabditis elegans / genetics* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Gene Knockdown Techniques Mutation Proteasome Endopeptidase Complex / metabolism Quality Control* Stress, Physiological Superoxide Dismutase / genetics Superoxide Dismutase-1 Transcription, Genetic / physiology* Tumor Suppressor Protein p53 / physiology* |
| IF | 7.076 |
| 引用数 | 21 |
| WOS 分野 | BIOLOGY 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 | X(Twitter) |
| 各媒体での言及数の合計 | 38 |
| 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 | |
| 線虫 | tm1380 |