{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T02:04:49Z","timestamp":1780625089352,"version":"3.54.1"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,8,13]],"date-time":"2015-08-13T00:00:00Z","timestamp":1439424000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,8,13]],"date-time":"2015-08-13T00:00:00Z","timestamp":1439424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The activation of nuclear factor kappa B (NF-\u03baB) signaling has a central role in the development of adult T-cell leukemia\/lymphoma (ATL) and many other cancers. However, the activation mechanism of the NF-\u03baB pathways remains poorly understood. Recently, we reported that N-myc downstream-regulated gene 2 (NDRG2) is a negative regulator of the phosphoinositide 3-kinase (PI3K)\/AKT pathway by promoting the active dephosphorylated form of PTEN at its C-terminus via the recruitment of PP2A. Additionally, the down-regulation of NDRG2 expression promotes the inactive phosphorylated form of PTEN, which results in constitutively active PI3K\/AKT signaling in various cancer cell types. Here, we investigated the involvement of NDRG2 in modulating NF-\u03baB signaling. The forced expression of NDRG2 in ATL cells down-regulates not only the canonical pathway by inhibiting AKT signaling but also the non-canonical pathway by inducing NF-\u03baB-inducing kinase (NIK) dephosphorylation via the recruitment of PP2A. Therefore, NDRG2 works as a PP2A recruiter to suppress not only PI3K\/AKT signaling but also NF-\u03baB signaling, which is particularly important in host defenses or immune responses to Human T-cell leukemia virus type 1 (HTLV-1) infection. Furthermore, the loss of NDRG2 expression might play an important role in the progression of tumor development after HTLV-1 infection.<\/jats:p>","DOI":"10.1038\/srep12841","type":"journal-article","created":{"date-parts":[[2015,8,13]],"date-time":"2015-08-13T09:54:31Z","timestamp":1439459671000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Loss of NDRG2 enhanced activation of the NF-\u03baB pathway by PTEN and NIK phosphorylation for ATL and other cancer development"],"prefix":"10.1038","volume":"5","author":[{"given":"Tomonaga","family":"Ichikawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shingo","family":"Nakahata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Fujii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidekatsu","family":"Iha","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":[[2015,8,13]]},"reference":[{"key":"BFsrep12841_CR1","doi-asserted-by":"publisher","first-page":"5952","DOI":"10.1038\/sj.onc.1208969","volume":"24","author":"Yamaoka,S Sun, S. 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