論文 - 詳細
| RRC ID | 43885 |
|---|---|
| 著者 | Moen EL, Wen S, Anwar T, Cross-Knorr S, Brilliant K, Birnbaum F, Rahaman S, Sedivy JM, Moss SF, Chatterjee D. |
| タイトル | Regulation of RKIP function by Helicobacter pylori in gastric cancer. |
| ジャーナル | PLoS One |
| Abstract |
Helicobacter pylori (H. pylori) is a gram-negative, spiral-shaped bacterium that infects more than half of the world's population and is a major cause of gastric adenocarcinoma. The mechanisms that link H. pylori infection to gastric carcinogenesis are not well understood. In the present study, we report that the Raf-kinase inhibitor protein (RKIP) has a role in the induction of apoptosis by H. pylori in gastric epithelial cells. Western blot and luciferase transcription reporter assays demonstrate that the pathogenicity island of H. pylori rapidly phosphorylates RKIP, which then localizes to the nucleus where it activates its own transcription and induces apoptosis. Forced overexpression of RKIP enhances apoptosis in H. pylori-infected cells, whereas RKIP RNA inhibition suppresses the induction of apoptosis by H. pylori infection. While inducing the phosphorylation of RKIP, H. pylori simultaneously targets non-phosphorylated RKIP for proteasome-mediated degradation. The increase in RKIP transcription and phosphorylation is abrogated by mutating RKIP serine 153 to valine, demonstrating that regulation of RKIP activity by H. pylori is dependent upon RKIP's S153 residue. In addition, H. pylori infection increases the expression of Snail, a transcriptional repressor of RKIP. Our results suggest that H. pylori utilizes a tumor suppressor protein, RKIP, to promote apoptosis in gastric cancer cells. |
| 巻・号 | 7(5) |
| ページ | e37819 |
| 公開日 | 2012-1-1 |
| DOI | 10.1371/journal.pone.0037819 |
| PII | PONE-D-12-00053 |
| PMID | 22662230 |
| PMC | PMC3360604 |
| MeSH | Antigens, Bacterial / metabolism Apoptosis / genetics Bacterial Proteins / metabolism Cell Line, Tumor Helicobacter Infections / metabolism* Helicobacter pylori / metabolism* Helicobacter pylori / pathogenicity Humans Interleukin-6 / pharmacology Phosphatidylethanolamine Binding Protein / genetics Phosphatidylethanolamine Binding Protein / metabolism* Phosphorylation / drug effects Protein Kinase C / metabolism Protein Stability Protein Transport STAT3 Transcription Factor / genetics STAT3 Transcription Factor / metabolism Snail Family Transcription Factors Stomach Neoplasms / genetics Stomach Neoplasms / metabolism* Transcription Factors / metabolism Transcription, Genetic / drug effects |
| IF | 2.74 |
| 引用数 | 11 |
| WOS 分野 | ONCOLOGY |
| 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 | Peer-review(Publons) |
| 各媒体での言及数の合計 | 2 |
| 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 | MKN28(RCB1000) |