論文 - 詳細
| RRC ID | 55887 |
|---|---|
| 著者 | Kanamoto M, Tsuchiya Y, Nakao Y, Suzuki T, Motohashi H, Yamamoto M, Kamata H. |
| タイトル | Structural instability of IκB kinase β promotes autophagic degradation through enhancement of Keap1 binding. |
| ジャーナル | PLoS One |
| Abstract |
IKKβ, an essential kinase of NF-κB signaling, is composed of an N-terminal kinase domain (KD) and a C-terminal scaffolding domain, containing a ubiquitin-like domain (ULD). The Hsp90 chaperon has special responsibility for folding of protein kinases including IKKβ. Here, we found that Hsp90 inhibition induced IKKβ degradation, which is partially mediated by Keap1. Geldanamycin (GA), a Hsp90 inhibitor, enhances association of IKKβ with Keap1 through the binding site in KD, and translocates IKKβ to detergent-insoluble fractions leading to its autophagic degradation. An electrophile tBHQ suppressed Keap1-mediated proteasomal Nrf2 degradation but not autophagic IKKβ degradation. Substitution mutation of Leu353 to Ala in the ULD destabilizes IKKβ, enhances its association with Keap1, translocates it to detergent-insoluble fractions, and causes its autophagic degradation. These results suggest that Keap1 is involved in the degradation of structural destabilized IKKβ and negative regulation of NF-κB under proteotoxic stress. |
| 巻・号 | 13(11) |
| ページ | e0203978 |
| 公開日 | 2018-11-30 |
| DOI | 10.1371/journal.pone.0203978 |
| PII | PONE-D-18-25233 |
| PMID | 30500824 |
| PMC | PMC6267955 |
| MeSH | Amino Acid Substitution Animals Autophagy* HEK293 Cells HSP90 Heat-Shock Proteins / genetics HSP90 Heat-Shock Proteins / metabolism Humans I-kappa B Kinase / genetics I-kappa B Kinase / metabolism* Kelch-Like ECH-Associated Protein 1 / genetics Kelch-Like ECH-Associated Protein 1 / metabolism* Mice Mice, Knockout Mutation, Missense NF-kappa B / genetics NF-kappa B / metabolism Protein Domains Protein Folding Protein Transport / genetics Proteolysis* |
| IF | 2.776 |
| 引用数 | 0 |
| 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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| 各媒体での言及数の合計 | 0 |
| 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 | 293(RCB1637) |