p53 attenuates AKT signaling by modulating membrane phospholipid composition

被引：41

作者：

Rueda-Rincon, Natalia ^{[1
]}

Bloch, Katarzyna ^{[1
]}

Derua, Rita ^{[2
]}

Vyas, Rajesh ^{[3
,4
]}

Harms, Amy ^{[5
,6
]}

Hankemeier, Thomas ^{[5
,6
]}

Khan, Niamat Ali ^{[1
]}

Dehairs, Jonas ^{[1
]}

Bagadi, Muralidhararao ^{[1
]}

Binda, Maria Mercedes ^{[7
]}

Waelkens, Etienne ^{[2
]}

Marine, Jean-Christophe ^{[3
,4
]}

Swinnen, Johannes V. ^{[1
]}

机构：

[1] Univ Leuven, KU Leuven, Dept Oncol, Lab Lipid Metab & Canc, Leuven, Belgium

[2] Univ Leuven, KU Leuven, Dept Cellular & Mol Med, Lab Prot Phosphorylat & Prote, Leuven, Belgium

[3] Univ Leuven, KU Leuven, Ctr Biol Dis, Lab Mol Canc Biol,VIB, Leuven, Belgium

[4] Univ Leuven, KU Leuven, Dept Human Genet, Lab Mol Canc Biol,VIB, Leuven, Belgium

[5] Univ Leuven, Leiden Acad Ctr Drug Res, Div Analyt Biosci, Leuven, Belgium

[6] Netherlands Metab Ctr, Leiden, Netherlands

[7] IREC, Pole Gynecol, Brussels, Belgium

来源：

ONCOTARGET | 2015年 / 6卷 / 25期

关键词：

p53; SCD; SREBP; phospholipids; cancer; COA DESATURASE 1; ELEMENT-BINDING PROTEIN; DE-NOVO LIPOGENESIS; CELL-CYCLE ARREST; CANCER-CELLS; LIPID-SYNTHESIS; INHIBITION; METABOLISM; ACTIVATION; TRANSCRIPTION;

D O I：

10.18632/oncotarget.4067

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：21240 / 21254

页数：15

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