title: Cofactor Strap regulates oxidative phosphorylation and mitochondrial p53 activity through ATP synthase.
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.
authors.affiliation: Laboratory of Cancer Biology, Department of Oncology, Medical Science Division, University of Oxford, Oxford, UK.
authors.forename: S
authors.initials: S
authors.lastname: Maniam
authors.affiliation: Laboratory of Cancer Biology, Department of Oncology, Medical Science Division, University of Oxford, Oxford, UK.
authors.forename: A S
authors.initials: AS
authors.lastname: Coutts
authors.affiliation: Department of Oncology, Medical Science Division, University of Oxford, Oxford, UK.
authors.forename: M R
authors.initials: MR
authors.lastname: Stratford
authors.affiliation: Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: J
authors.initials: J
authors.lastname: McGouran
authors.affiliation: Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: B
authors.initials: B
authors.lastname: Kessler
authors.affiliation: Laboratory of Cancer Biology, Department of Oncology, Medical Science Division, University of Oxford, Oxford, UK.
authors.forename: N B
authors.initials: NB
authors.lastname: La Thangue
mesh_terms: D017209:Apoptosis / Q000502:physiology; D005947:Glucose / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D025261:Mitochondrial Proton-Translocating ATPases; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption / Q000502:physiology*; D016601:RNA-Binding Proteins; D015533:Transcriptional Activation / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; C403447:STRAP protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D025261:Mitochondrial Proton-Translocating ATPases; D005947:Glucose