p53 attenuates AKT signaling by modulating membrane phospholipid composition

Natalia Rueda-Rincon, Katarzyna Bloch, Rita Derua, Rajesh Vyas, Amy Harms, Thomas Hankemeier, Niamat Ali Khan, Jonas Dehairs, Muralidhararao Bagadi, Maria Mercedes Binda, Etienne Waelkens, Jean Christophe Marine, Johannes V. Swinnen

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

The p53 tumor suppressor is the central component of a complex network of signaling pathways that protect organisms against the propagation of cells carrying oncogenic mutations. Here we report a previously unrecognized role of p53 in membrane phospholipids composition. By repressing the expression of stearoyl-CoA desaturase 1, SCD, the enzyme that converts saturated to mono-unsaturated fatty acids, p53 causes a shift in the content of phospholipids with mono-unsaturated acyl chains towards more saturated phospholipid species, particularly of the phosphatidylinositol headgroup class. This shift affects levels of phosphatidylinositol phosphates, attenuates the oncogenic AKT pathway, and contributes to the p53- mediated control of cell survival. These findings expand the p53 network to phospholipid metabolism and uncover a new molecular pathway connecting p53 to AKT signaling.

Original languageEnglish (US)
Pages (from-to)21240-21254
Number of pages15
JournalOncotarget
Volume6
Issue number25
DOIs
StatePublished - 2015

Keywords

  • Cancer
  • Phospholipids
  • SCD
  • SREBP
  • p53

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