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Title :Degradation of p47 by autophagy contributes to CADM1 overexpression in ATLL cells through the activation of NF-κB
Authors :Sarkar, Bidhan
Nishikata, Ichiro
Nakahata, Shingo
Ichikawa, Tomonaga
Shiraga, Toshiyuki
Saha, Hashi Rani
Tanaka, Yuetsu
Shimoda, Kazuya
Morishita, Kazuhiro
Issue Date :5-Mar-2019
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.
URL :https://doi.org/10.1038/s41598-019-39424-7
Type Local :雑誌掲載論文
ISSN :2045-2322
Publisher :Springer Nature
URI :http://hdl.handle.net/20.500.12000/45626
Citation :Scientific Reports Vol.9 no.3491
Appears in Collections:Peer-reviewed Journal Articles (Faculty of Medicine)

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