ROS-mediated p53 induction of Lpin1 regulates fatty acid oxidation in response to nutritional stress.
Mol Cell
; 44(3): 491-501, 2011 Nov 04.
Article
em En
| MEDLINE
| ID: mdl-22055193
ABSTRACT
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 fld 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfatidato Fosfatase
/
Proteínas Nucleares
/
Estado Nutricional
/
Proteína Supressora de Tumor p53
/
Espécies Reativas de Oxigênio
/
Estresse Oxidativo
/
Mioblastos
/
Metabolismo Energético
/
Ácidos Graxos
/
Glucose
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Cell
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Canadá