> Detailanzeige

Warnier, Marine; Flaman, Jean‐Michel; Chouabe, Christophe; Wiel, Clotilde; Gras, Baptiste; Griveau, Audrey; Blanc, Elena; Foy, Jean‐Philippe; Mathot, Pauline; Saintigny, Pierre; Van Coppenolle, Fabien; Vindrieux, David; Martin, Nadine; Bernard, David

The SCN9A channel and plasma membrane depolarization promote cellular senescence through Rb pathway

Literatur-
verwaltung

Zur
Merkliste

Lösche von
Merkliste

Per Whatsapp teilen

Schließen

Merkliste



Sie können Bookmarks mittels Listen verwalten, loggen Sie sich dafür bitte in Ihr SLUB Benutzerkonto ein.
  • Medientyp: E-Artikel
  • Titel: The SCN9A channel and plasma membrane depolarization promote cellular senescence through Rb pathway
  • Beteiligte: Warnier, Marine; Flaman, Jean‐Michel; Chouabe, Christophe; Wiel, Clotilde; Gras, Baptiste; Griveau, Audrey; Blanc, Elena; Foy, Jean‐Philippe; Mathot, Pauline; Saintigny, Pierre; Van Coppenolle, Fabien; Vindrieux, David; Martin, Nadine; Bernard, David
  • Erschienen: Wiley, 2018
  • Erschienen in: Aging Cell
  • Sprache: Englisch
  • DOI: 10.1111/acel.12736
  • ISSN: 1474-9726; 1474-9718
  • Schlagwörter: Cell Biology ; Aging
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Summary</jats:title><jats:p>Oncogenic signals lead to premature senescence in normal human cells causing a proliferation arrest and the elimination of these defective cells by immune cells. Oncogene‐induced senescence (<jats:styled-content style="fixed-case">OIS</jats:styled-content>) prevents aberrant cell division and tumor initiation. In order to identify new regulators of <jats:styled-content style="fixed-case">OIS</jats:styled-content>, we performed a loss‐of‐function genetic screen and identified that the loss of <jats:styled-content style="fixed-case">SCN</jats:styled-content>9A allowed cells to escape from <jats:styled-content style="fixed-case">OIS</jats:styled-content>. The expression of this sodium channel increased in senescent cells during <jats:styled-content style="fixed-case">OIS</jats:styled-content>. This upregulation was mediated by <jats:styled-content style="fixed-case">NF</jats:styled-content>‐κB transcription factors, which are well‐known regulators of senescence. Importantly, the induction of <jats:styled-content style="fixed-case">SCN</jats:styled-content>9A by an oncogenic signal or by p53 activation led to plasma membrane depolarization, which in turn, was able to induce premature senescence. Computational and experimental analyses revealed that <jats:styled-content style="fixed-case">SCN</jats:styled-content>9A and plasma membrane depolarization mediated the repression of mitotic genes through a calcium/Rb/E2F pathway to promote senescence. Taken together, our work delineates a new pathway, which involves the <jats:styled-content style="fixed-case">NF</jats:styled-content>‐κB transcription factor, <jats:styled-content style="fixed-case">SCN</jats:styled-content>9A expression, plasma membrane depolarization, increased calcium, the Rb/E2F pathway and mitotic gene repression in the regulation of senescence. This work thus provides new insight into the involvement of ion channels and plasma membrane potential in the control of senescence.</jats:p>
  • Zugangsstatus: Freier Zugang