論文 - 詳細
| RRC ID | 38135 |
|---|---|
| 著者 | Ichikawa T, Nakahata S, Fujii M, Iha H, Morishita K. |
| タイトル | Loss of NDRG2 enhanced activation of the NF-κB pathway by PTEN and NIK phosphorylation for ATL and other cancer development. |
| ジャーナル | Sci Rep |
| Abstract |
The activation of nuclear factor kappa B (NF-κB) signaling has a central role in the development of adult T-cell leukemia/lymphoma (ATL) and many other cancers. However, the activation mechanism of the NF-κB pathways remains poorly understood. Recently, we reported that N-myc downstream-regulated gene 2 (NDRG2) is a negative regulator of the phosphoinositide 3-kinase (PI3K)/AKT pathway by promoting the active dephosphorylated form of PTEN at its C-terminus via the recruitment of PP2A. Additionally, the down-regulation of NDRG2 expression promotes the inactive phosphorylated form of PTEN, which results in constitutively active PI3K/AKT signaling in various cancer cell types. Here, we investigated the involvement of NDRG2 in modulating NF-κB signaling. The forced expression of NDRG2 in ATL cells down-regulates not only the canonical pathway by inhibiting AKT signaling but also the non-canonical pathway by inducing NF-κB-inducing kinase (NIK) dephosphorylation via the recruitment of PP2A. Therefore, NDRG2 works as a PP2A recruiter to suppress not only PI3K/AKT signaling but also NF-κB signaling, which is particularly important in host defenses or immune responses to Human T-cell leukemia virus type 1 (HTLV-1) infection. Furthermore, the loss of NDRG2 expression might play an important role in the progression of tumor development after HTLV-1 infection. |
| 巻・号 | 5 |
| ページ | 12841 |
| 公開日 | 2015-8-13 |
| DOI | 10.1038/srep12841 |
| PII | srep12841 |
| PMID | 26269411 |
| PMC | PMC4534796 |
| MeSH | Adult Cell Line, Tumor Gene Expression Regulation, Leukemic Human T-lymphotropic virus 1 / genetics Human T-lymphotropic virus 1 / pathogenicity Humans Leukemia-Lymphoma, Adult T-Cell / genetics* Leukemia-Lymphoma, Adult T-Cell / pathology Leukemia-Lymphoma, Adult T-Cell / virology NF-kappa B / genetics PTEN Phosphohydrolase / biosynthesis PTEN Phosphohydrolase / genetics* Phosphatidylinositol 3-Kinases / genetics Phosphorylation Protein Serine-Threonine Kinases / biosynthesis Protein Serine-Threonine Kinases / genetics* Proto-Oncogene Proteins c-akt / genetics Signal Transduction Tumor Suppressor Proteins / biosynthesis Tumor Suppressor Proteins / genetics* |
| IF | 3.998 |
| 引用数 | 25 |
| WOS 分野 | 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 | 1 |
| 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) |