Oncotarget

Research Papers:

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 and Johannes V. Swinnen

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Oncotarget. 2015; 6:21240-21254. https://doi.org/10.18632/oncotarget.4067

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Abstract

Natalia Rueda-Rincon1, Katarzyna Bloch1, Rita Derua2, Rajesh Vyas3,4, Amy Harms5,6, Thomas Hankemeier5,6, Niamat Ali Khan1, Jonas Dehairs1, Muralidhararao Bagadi1, Maria Mercedes Binda7, Etienne Waelkens2, Jean-Christophe Marine3,4, Johannes V. Swinnen1

1KU Leuven - University of Leuven, Department of Oncology, Laboratory of Lipid Metabolism and Cancer, Leuven, Belgium

2KU Leuven - University of Leuven, Department of Cellular and Molecular Medicine, Laboratory of Protein Phosphorylation and Proteomics, Leuven, Belgium

3KU Leuven - University of Leuven, Center for the Biology of Disease, Laboratory for Molecular Cancer Biology, VIB, Leuven, Belgium

4KU Leuven - University of Leuven, Department of Human Genetics, Laboratory for Molecular Cancer Biology, VIB, Leuven, Belgium

5Division of Analytical Biosciences, Leiden Academic Centre for Drug Research, Leiden University, The Netherlands

6Netherlands Metabolomics Centre, Leiden, The Netherlands

7Institut de Recherche Expérimentale et Clinique (IREC), Pôle de Gynécologie, Bruxelles, Belgium

Correspondence to:

Johannes V. Swinnen, e-mail: johan.swinnen@med.kuleuven.be

Keywords: p53, SCD, SREBP, phospholipids, cancer

Received: February 03, 2015     Accepted: May 21, 2015     Published: June 03, 2015

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.


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