p53 regulates glucose metabolism through an IKK-NF-kappaB pathway and inhibits cell transformation.
Nat Cell Biol
; 10(5): 611-8, 2008 May.
Article
en En
| MEDLINE
| ID: mdl-18391940
ABSTRACT
Cancer cells use aerobic glycolysis preferentially for energy provision and this metabolic change is important for tumour growth. Here, we have found a link between the tumour suppressor p53, the transcription factor NF-kappaB and glycolysis. In p53-deficient primary cultured cells, kinase activities of IKKalpha and IKKbeta and subsequent NF-kappaB activity were enhanced. Activation of NF-kappaB, by loss of p53, caused an increase in the rate of aerobic glycolysis and upregulation of Glut3. Oncogenic Ras-induced cell transformation and acceleration of aerobic glycolysis in p53-deficient cells were suppressed in the absence of p65/NF-kappaB expression, and were restored by GLUT3 expression. It was also shown that a glycolytic inhibitor diminished the enhanced IKK activity in p53-deficient cells. Moreover, in Ras-expressing p53-deficient cells, IKK activity was suppressed by p65 deficiency and restored by GLUT3 expression. Taken together, these data indicate that p53 restricts activation of the IKK-NF-kappaB pathway through suppression of glycolysis. These results suggest that a positive-feedback loop exists, whereby glycolysis drives IKK-NF-kappaB activation, and that hyperactivation of this loop by loss of p53 is important in oncogene-induced cell transformation.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Transformación Celular Neoplásica
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Proteína p53 Supresora de Tumor
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Quinasa I-kappa B
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Factor de Transcripción ReIA
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Glucosa
Límite:
Animals
Idioma:
En
Revista:
Nat Cell Biol
Año:
2008
Tipo del documento:
Article
País de afiliación:
Japón