Cofactor Strap regulates oxidative phosphorylation and mitochondrial p53 activity through ATP synthase.
Cell Death Differ
; 22(1): 156-63, 2015 Jan.
Article
em En
| MEDLINE
| ID: mdl-25168243
ABSTRACT
Metabolic reprogramming is a hallmark of cancer cells. Strap (stress-responsive activator of p300) is a novel TPR motif OB-fold protein that contributes to p53 transcriptional activation. We show here that, in addition to its established transcriptional role, Strap is localised at mitochondria where one of its key interaction partners is ATP synthase. Significantly, the interaction between Strap and ATP synthase downregulates mitochondrial ATP production. Under glucose-limiting conditions, cancer cells are sensitised by mitochondrial Strap to apoptosis, which is rescued by supplementing cells with an extracellular source of ATP. Furthermore, Strap augments the apoptotic effects of mitochondrial p53. These findings define Strap as a dual regulator of cellular reprogramming first as a nuclear transcription cofactor and second in the direct regulation of mitochondrial respiration.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosforilação Oxidativa
/
Consumo de Oxigênio
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Proteína Supressora de Tumor p53
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Mitocôndrias
/
Proteínas de Neoplasias
Limite:
Humans
Idioma:
En
Revista:
Cell Death Differ
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Reino Unido