| 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
|
| リソース情報 |
| ヒト・動物細胞 |
293T(RCB2202) |
