ROS-Mediated p53 Induction of Lpin1 Regulates Fatty Acid Oxidation in Response to Nutritional Stress

被引：167

作者：

Assaily, Wissam ^{[1
,2
]}

Rubinger, Daniel A. ^{[1
]}

Wheaton, Keith ^{[1
]}

Lin, Yunping ^{[1
]}

Ma, Weili ^{[1
]}

Xuan, Wanli ^{[1
]}

Brown-Endres, Lauren ^{[2
]}

Tsuchihara, Katsuya ^{[3
]}

Mak, Tak W. ^{[2
,3
]}

Benchimol, Samuel ^{[1
]}

机构：

[1] York Univ, Dept Biol, Toronto, ON M3J 1P3, Canada

[2] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2M9, Canada

[3] Univ Hlth Network, Princess Margaret Hosp, Campbell Family Inst Breast Canc Res, Toronto, ON M5G 2M9, Canada

来源：

MOLECULAR CELL | 2011年 / 44卷 / 03期

关键词：

ACTIVATED PROTEIN-KINASE; DNA-DAMAGE; P53-INDUCIBLE REGULATOR; GENE-EXPRESSION; ATM ACTIVATION; NUCLEAR FOCI; IN-VIVO; LIPIN; METABOLISM; PATHWAYS;

D O I：

10.1016/j.molcel.2011.08.038

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The p53 protein is activated by stress signals and exhibits both protective and death-promoting functions that are considered important for its tumor suppressor function. Emerging evidence points toward an additional role for p53 in metabolism. Here, we identify Lpin1 as a p53-responsive gene that is induced in response to DNA damage and glucose deprivation. Lpin1 is essential for adipocyte development and fat metabolism, and mutation in this gene is responsible for the lypodystrophy phenotype in fid mice. We show that p53 and Lpin1 regulate fatty acid oxidation in mouse C2C12 myoblasts. p53 phosphorylation on Ser18 in response to low glucose is ROS and ATM dependent. Lpin1 expression in response to nutritional stress is controlled through the ROS-ATM-p53 pathway and is conserved in human cells. Lpin1 provides a critical link between p53 and metabolism that may be an important component in mediating the tumor suppressor function of p53.

引用

页码：491 / 501

页数：11

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