Degradation of p47 by autophagy contributes to CADM1 overexpression in ATLL cells through the activation of NF-κB

• Published in: Scientific reports 2019-03, Vol.9 (1), p.3491-3491, Article 3491
• Main Authors: Sarkar, Bidhan, Nishikata, Ichiro, Nakahata, Shingo, Ichikawa, Tomonaga, Shiraga, Toshiyuki, Saha, Hasi Rani, Fujii, Masahiro, Tanaka, Yuetsu, Shimoda, Kazuya, Morishita, Kazuhiro
• Format: Article
• Language: English
• Subjects: 13/95; 631/67; 692/4017; 96/109; Autophagy; Cell activation; Cell adhesion & migration; Cell adhesion molecules; Cell surface; Humanities and Social Sciences; Leukemia; Lymphocytes T; Lymphoma; multidisciplinary; NF-κB protein; Phagocytosis; Science; Science (multidisciplinary); Signal transduction; Surface markers; T cell receptors; Transcription
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-39424-7

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.