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Kawamura, K.* ; Ono, K. ; Mishima, E. ; Hashizume, O.* ; Conrad, M. ; Miki, H.* ; Funato, Y.*

Cellular Mg2+ decrease causes a distinctive NF-κB-dependent form of cell death.

Cell Rep. 45:116964 (2026)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Mg2+ is an essential cofactor for numerous enzymes, supporting fundamental cellular processes. The phosphatase of regenerating liver (PRL) protein family, frequently upregulated in cancer, inhibits cyclin M (CNNM) Mg2+ efflux transporters. To elucidate the physiological role of PRL in Mg2+ homeostasis at the cellular level, we employed combined genetic knockout and knockdown approaches. PRL deletion led to marked reduction of intracellular Mg2+ levels and triggered extensive cell death. Transcriptomic analysis revealed activation of the NF-κB pathway, and, accordingly, the genetic deletion of NF-κB p65 subunit abrogated cell death. Similarly, CNNM overexpression triggered intracellular Mg2+ decrease, NF-κB activation, and subsequent cell death. Notably, this form of cell death exhibited characteristic morphological features, including actin-driven fiber-like protrusions, distinguishing it from known cell death modalities. Our findings uncover a distinct mode of NF-κB-dependent cell death triggered by intracellular Mg2+ decrease.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Cnnm ; Cp: Cell Biology ; Nf-κb ; Prl ; Actin Polymerization ; Magnesium ; Regulated Cell Death; Salmonella-typhimurium; Magnesium Transport; Mg2+ Transporter; Cancer; Protein; Phosphatase; Inhibitor; Pathway; Influx; Trpm6
ISSN (print) / ISBN 2211-1247
e-ISSN 2211-1247
Journal Cell Reports
Quellenangaben Volume: 45, Issue: 2, Pages: , Article Number: 116964 Supplement: ,
Publisher Elsevier
Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Reviewing status Peer reviewed
Institute(s) Institute of Metabolism and Cell Death (MCD)
Grants European Research Council (ERC)
JST FOREST program
JST SPRING program
JSPS KAKENHI