セキ　タカオ   Seki Takao   関　崇生    所属   東邦大学  医学部 医学科    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	The Nuclear Export Signal of IκBα Drives RelB Oscillations in the Noncanonical NF-κB Pathway.
掲載誌名	正式名：Genes to cells : devoted to molecular & cellular mechanisms 略　 称：Genes Cells ISSNコード：13569597/13652443
掲載区分	国外
出版社	Wiley
巻・号・頁	31(4)
総ページ数	12
国際共著	国際共著
著者・共著者	Takao Seki, Shelly Davis, Shigeki Miyamoto, Taishin Akiyama, Hiroyasu Nakano, Jun-ichiro Inoue, Katsuhide Okunishi
担当区分	筆頭著者,責任著者
発行年月	2026/07/02
概要	The noncanonical NF-κB pathway regulates immune development and inflammation through RelB nuclear translocation, yet the dynamics of this process at the single-cell level remain poorly understood. Using live-cell imaging of RelB-Venus knock-in mouse embryonic fibroblasts, we show that LTβR or TWEAK stimulation induces four distinct RelB nuclear translocation patterns: oscillating, prolonged activation, transient activation, and non-responding. Approximately 40% of cells exhibited oscillatory behavior with a predominant period of 1.5–2.0 h, similar to RelA oscillations in the canonical pathway. Mechanistically, RelB oscillations required CRM1-mediated nuclear export, ongoing protein synthesis, NIK-dependent noncanonical signaling, and the IκBα nuclear export signal. Knockdown or knockout of Nfkb2 (encoding p100) induced spontaneous RelB oscillations without stimulation, identifying p100 as a threshold regulator that controls oscillation probability through cytoplasmic sequestration of RelB. Co-immunoprecipitation analysis revealed dynamic RelB-IκBα complex formation in both cytoplasmic and nuclear fractions following LTβR stimulation. Furthermore, disruption of RelB oscillations in NfkbiaNES/NES cells was associated with impaired induction of NF-κB target genes. These findings provide the first experimental characterization of RelB oscillatory dynamics and reveal both conserved and pathway-specific mechanisms governing noncanonical NF-κB signaling.
researchmap用URL	https://onlinelibrary.wiley.com/doi/10.1111/gtc.70135