論文 - 詳細
| RRC ID | 54901 |
|---|---|
| 著者 | Sarkar B, Nishikata I, Nakahata S, Ichikawa T, Shiraga T, Saha HR, Fujii M, Tanaka Y, Shimoda K, Morishita K. |
| タイトル | Degradation of p47 by autophagy contributes to CADM1 overexpression in ATLL cells through the activation of NF-κB. |
| ジャーナル | Sci Rep |
| Abstract |
Cell adhesion molecule 1 (CADM1), a member of the immunoglobulin superfamily, is identified as a novel cell surface marker for human T-cell leukemia virus (HTLV-1)-infected T cells. Adult T-cell leukemia/lymphoma (ATLL) is developed in HTLV-1-infected T-cells after a long infection period. To examine the mechanism of CADM1 overexpression in ATLL, we first identified that CADM1 is transcriptionally up-regulated by a transcriptional enhancer element through NF-κB signaling pathway. In HTLV-1-infected T-cells, CADM1 expression is dependent on HTLV-1/Tax through activation of canonical and non-canonical NF-κB; however, in ATLL cells with frequent loss of Tax expression, the activation of canonical NF-κB only enhances the CADM1 expression. Along with active mutations in signaling molecules under T-cell recepor (TCR) signaling, degradation of p47, a negative regulator of NF-κB, was essential for activation of canonical NF-κB through stabilization of NEMO (NF-κB essential modulator). The mechanism of p47 degradation is primarily dependent on activation of lysosomal-autophagy and the autophagy is activated in most of the HTLV-infected and ATLL cells, suggesting that the p47 degradation may be a first key molecular event during HTLV-1 infection to T-cells as a connector of two important signaling pathways, NF-κB and autophagy. |
| 巻・号 | 9(1) |
| ページ | 3491 |
| 公開日 | 2019-3-5 |
| DOI | 10.1038/s41598-019-39424-7 |
| PII | 10.1038/s41598-019-39424-7 |
| PMID | 30837480 |
| PMC | PMC6400899 |
| MeSH | Adaptor Proteins, Signal Transducing / genetics Adaptor Proteins, Signal Transducing / metabolism* Autophagy* Binding Sites Cell Adhesion Molecule-1 / genetics Cell Adhesion Molecule-1 / metabolism* Cell Line, Tumor Down-Regulation Gene Products, tax / metabolism Human T-lymphotropic virus 1 / pathogenicity Humans Jurkat Cells Leukemia-Lymphoma, Adult T-Cell / metabolism Leukemia-Lymphoma, Adult T-Cell / pathology* Lysosomes / metabolism NF-kappa B / metabolism* Promoter Regions, Genetic Signal Transduction Transcriptional Activation Up-Regulation |
| IF | 4.011 |
| 引用数 | 4 |
| 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 | 5 |
| 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 | 293T(RCB2202) |