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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-\u03baB signaling pathway. In HTLV-1-infected T-cells, CADM1 expression is dependent on HTLV-1\/Tax through activation of canonical and non-canonical NF-\u03baB; however, in ATLL cells with frequent loss of Tax expression, the activation of canonical NF-\u03baB 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-\u03baB, was essential for activation of canonical NF-\u03baB through stabilization of NEMO (NF-\u03baB 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-\u03baB and autophagy.<\/jats:p>","DOI":"10.1038\/s41598-019-39424-7","type":"journal-article","created":{"date-parts":[[2019,3,5]],"date-time":"2019-03-05T11:05:48Z","timestamp":1551783948000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Degradation of p47 by autophagy contributes to CADM1 overexpression in ATLL cells through the activation of NF-\u03baB"],"prefix":"10.1038","volume":"9","author":[{"given":"Bidhan","family":"Sarkar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ichiro","family":"Nishikata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shingo","family":"Nakahata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomonaga","family":"Ichikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Shiraga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasi Rani","family":"Saha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Fujii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuetsu","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Shimoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Morishita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,3,5]]},"reference":[{"key":"39424_CR1","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1016\/S1470-2045(14)70202-5","volume":"11","author":"K Ishitsuka","year":"2014","unstructured":"Ishitsuka, K. & Tamura, K. 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