論文 - 詳細
| RRC ID | 61346 |
|---|---|
| 著者 | Colleran A, Ryan A, O'Gorman A, Mureau C, Liptrot C, Dockery P, Fearnhead H, Egan LJ. |
| タイトル | Autophagosomal IkappaB alpha degradation plays a role in the long term control of tumor necrosis factor-alpha-induced nuclear factor-kappaB (NF-kappaB) activity. |
| ジャーナル | J Biol Chem |
| Abstract |
Transcription factor NF-κB is persistently activated in many chronic inflammatory diseases and cancers. The short term regulation of NF-κB is well understood, but little is known about the mechanisms of its long term activation. We studied the effect of a single application of TNF-α on NF-κB activity for up to 48 h in intestinal epithelial cells. Results show that NF-κB remained persistently activated up to 48 h after TNF-α and that the long term activation of NF-κB was accompanied by a biphasic degradation of IκBα. The first phase of IκBα degradation was proteasome-dependent, but the second was not. Further investigation showed that TNF-α stimulated formation of autophagosomes in intestinal epithelial cells and that IκBα co-localized with autophagosomal vesicles. Pharmacological or genetic blockade of autophagosome formation or the inhibition of lysosomal proteases decreased TNF-α-induced degradation of IκBα and lowered NF-κB target gene expression. Together, these findings indicate a role of autophagy in the control of long term NF-κB activity. Because abnormalities in autophagy have been linked to ineffective innate immunity, we propose that alterations in NF-κB may mediate this effect. |
| 巻・号 | 286(26) |
| ページ | 22886-93 |
| 公開日 | 2011-7-1 |
| DOI | 10.1074/jbc.M110.199950 |
| PII | S0021-9258(19)48826-1 |
| PMID | 21454695 |
| PMC | PMC3123056 |
| MeSH | Animals Autophagy / physiology* Humans I-kappa B Proteins / genetics I-kappa B Proteins / immunology I-kappa B Proteins / metabolism* Immunity, Innate / physiology Mice Mice, Knockout NF-KappaB Inhibitor alpha NF-kappa B / genetics NF-kappa B / immunology NF-kappa B / metabolism* NIH 3T3 Cells Phagosomes / genetics Phagosomes / immunology Phagosomes / metabolism* Time Factors Tumor Necrosis Factor-alpha / genetics Tumor Necrosis Factor-alpha / immunology Tumor Necrosis Factor-alpha / metabolism* |
| IF | 4.238 |
| 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 |
| リソース情報 | |
| ヒト・動物細胞 | Atg5^(+/+)MEF(RCB2710) Atg5^(-/-)MEF(RCB2711) |