p53 negatively regulates transcription of the pyruvate dehydrogenase kinase Pdk2.
Cancer Res
; 72(2): 560-7, 2012 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-22123926
ABSTRACT
In cancer cells, the aberrant conversion of pyruvate into lactate instead of acetyl-CoA in the presence of oxygen is known as the Warburg effect. The consequences and mechanisms of this metabolic peculiarity are incompletely understood. Here we report that p53 status is a key determinant of the Warburg effect. Wild-type p53 expression decreased levels of pyruvate dehydrogenase kinase-2 (Pdk2) and the product of its activity, the inactive form of the pyruvate dehydrogenase complex (P-Pdc), both of which are key regulators of pyruvate metabolism. Decreased levels of Pdk2 and P-Pdc in turn promoted conversion of pyruvate into acetyl-CoA instead of lactate. Thus, wild-type p53 limited lactate production in cancer cells unless Pdk2 could be elevated. Together, our results established that wild-type p53 prevents manifestation of the Warburg effect by controlling Pdk2. These findings elucidate a new mechanism by which p53 suppresses tumorigenesis acting at the level of cancer cell metabolism.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteína Supressora de Tumor p53
/
Proteínas Serina-Treonina Quinases
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article