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Cofactor Strap regulates oxidative phosphorylation and mitochondrial p53 activity through ATP synthase
S Maniam1, A S Coutts1, M R Stratford2
1Laboratory of Cancer Biology, Department of Oncology, Medical Science Division, University of Oxford, Oxford, UK.
Cell Death and Differentiation
|August 30, 2014
Summary
Stress-responsive activator of p300 (Strap) protein regulates cancer cell metabolism. Strap’s novel mitochondrial role enhances apoptosis under glucose deprivation by downregulating ATP production.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Metabolic reprogramming is a key characteristic of cancer cells.
- Stress-responsive activator of p300 (Strap) is a protein involved in p53 transcriptional activation.
- The precise functions of Strap beyond nuclear transcription are not fully understood.
Purpose of the Study:
- To investigate the role of Strap in cellular metabolism and apoptosis.
- To identify novel interaction partners and cellular localization of Strap.
- To elucidate the impact of Strap on mitochondrial function and cancer cell survival.
Main Methods:
- Immunofluorescence and co-immunoprecipitation assays to determine Strap localization and interactions.
- Measurement of mitochondrial ATP production.
- Assessment of apoptosis in cancer cells under varying glucose and ATP conditions.
- Analysis of p53-mediated apoptosis.
Main Results:
- Strap is localized in mitochondria, interacting with ATP synthase.
- Strap binding to ATP synthase downregulates mitochondrial ATP production.
- Mitochondrial Strap sensitizes cancer cells to apoptosis under glucose-limiting conditions.
- Extracellular ATP supplementation rescues cells from Strap-induced apoptosis.
- Strap enhances the pro-apoptotic effects of mitochondrial p53.
Conclusions:
- Strap acts as a dual regulator of cellular reprogramming, influencing both nuclear transcription and mitochondrial respiration.
- Strap's mitochondrial function offers a potential therapeutic target for sensitizing cancer cells to apoptosis.
- The interaction between Strap and ATP synthase highlights a novel mechanism in cancer cell metabolic control.
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