論文 - 詳細
| RRC ID | 44931 |
|---|---|
| 著者 | Nakahata S, Ichikawa T, Maneesaay P, Saito Y, Nagai K, Tamura T, Manachai N, Yamakawa N, Hamasaki M, Kitabayashi I, Arai Y, Kanai Y, Taki T, Abe T, Kiyonari H, Shimoda K, Ohshima K, Horii A, Shima H, Taniwaki M, Yamaguchi R, Morishita K. |
| タイトル | Loss of NDRG2 expression activates PI3K-AKT signalling via PTEN phosphorylation in ATLL and other cancers. |
| ジャーナル | Nat Commun |
| Abstract |
Constitutive phosphatidylinositol 3-kinase (PI3K)-AKT activation has a causal role in adult T-cell leukaemia-lymphoma (ATLL) and other cancers. ATLL cells do not harbour genetic alterations in PTEN and PI3KCA but express high levels of PTEN that is highly phosphorylated at its C-terminal tail. Here we report a mechanism for the N-myc downstream-regulated gene 2 (NDRG2)-dependent regulation of PTEN phosphatase activity via the dephosphorylation of PTEN at the Ser380, Thr382 and Thr383 cluster within the C-terminal tail. We show that NDRG2 is a PTEN-binding protein that recruits protein phosphatase 2A (PP2A) to PTEN. The expression of NDRG2 is frequently downregulated in ATLL, resulting in enhanced phosphorylation of PTEN at the Ser380/Thr382/Thr383 cluster and enhanced activation of the PI3K-AKT pathway. Given the high incidence of T-cell lymphoma and other cancers in NDRG2-deficient mice, PI3K-AKT activation via enhanced PTEN phosphorylation may be critical for the development of cancer. |
| 巻・号 | 5 |
| ページ | 3393 |
| 公開日 | 2014-2-26 |
| DOI | 10.1038/ncomms4393 |
| PII | ncomms4393 |
| PMID | 24569712 |
| PMC | PMC3948061 |
| MeSH | Adult Animals Blotting, Western Cell Line, Tumor Gene Expression Regulation, Neoplastic HEK293 Cells Humans Jurkat Cells Leukemia-Lymphoma, Adult T-Cell / genetics Leukemia-Lymphoma, Adult T-Cell / metabolism Leukemia-Lymphoma, Adult T-Cell / pathology Mice Mice, Inbred C57BL Mice, Inbred ICR Mice, Knockout Microscopy, Confocal NIH 3T3 Cells Neoplasms / genetics Neoplasms / metabolism Neoplasms / pathology PTEN Phosphohydrolase / genetics PTEN Phosphohydrolase / metabolism* Phosphatidylinositol 3-Kinases / genetics Phosphatidylinositol 3-Kinases / metabolism* Phosphorylation Proto-Oncogene Proteins c-akt / genetics Proto-Oncogene Proteins c-akt / metabolism* RNA Interference Reverse Transcriptase Polymerase Chain Reaction Signal Transduction* Tumor Cells, Cultured Tumor Suppressor Proteins / genetics Tumor Suppressor Proteins / metabolism* |
| IF | 12.121 |
| 引用数 | 84 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | KLM-1(RCB2138) PK-45P(RCB2141) SAS(RCB1974) HO-1-u-1(RCB2102) Ca9-22(RCB1976) HSC-2(RCB1945) HSC-3(RCB1975) HSC-4(RCB1902) Sa3(RCB0980) HeLa 293T(RCB2202) NIH3T3 |