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Cofactor strap regulates oxidative phosphorylation and mitochondrial p53 activity through ATP synthase

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...

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Main Authors: Maniam, Sandra, Coutts, Amanda S., Stratford, Michael R. L., McGouran, Joanna F., Kessler, Benedikit M., La Thangue, N. B.
Format: Article
Language:English
Published: Nature Publishing Group 2015
Online Access:http://psasir.upm.edu.my/id/eprint/44087/1/Cofactor%20strap%20regulates%20oxidative%20phosphorylation%20and%20mitochondrial%20p53%20activity%20through%20ATP%20synthase.pdf
http://psasir.upm.edu.my/id/eprint/44087/
https://www.nature.com/articles/cdd2014135
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spelling my.upm.eprints.440872022-03-11T04:42:46Z http://psasir.upm.edu.my/id/eprint/44087/ Cofactor strap regulates oxidative phosphorylation and mitochondrial p53 activity through ATP synthase Maniam, Sandra Coutts, Amanda S. Stratford, Michael R. L. McGouran, Joanna F. Kessler, Benedikit M. La Thangue, N. B. 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. Nature Publishing Group 2015 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/44087/1/Cofactor%20strap%20regulates%20oxidative%20phosphorylation%20and%20mitochondrial%20p53%20activity%20through%20ATP%20synthase.pdf Maniam, Sandra and Coutts, Amanda S. and Stratford, Michael R. L. and McGouran, Joanna F. and Kessler, Benedikit M. and La Thangue, N. B. (2015) Cofactor strap regulates oxidative phosphorylation and mitochondrial p53 activity through ATP synthase. Cell Death and Differentiation, 22. pp. 156-163. ISSN 1350-9047; ESSN: 1476-5403 https://www.nature.com/articles/cdd2014135 10.1038/cdd.2014.135
institution Universiti Putra Malaysia
building UPM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Putra Malaysia
content_source UPM Institutional Repository
url_provider http://psasir.upm.edu.my/
language English
description 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.
format Article
author Maniam, Sandra
Coutts, Amanda S.
Stratford, Michael R. L.
McGouran, Joanna F.
Kessler, Benedikit M.
La Thangue, N. B.
spellingShingle Maniam, Sandra
Coutts, Amanda S.
Stratford, Michael R. L.
McGouran, Joanna F.
Kessler, Benedikit M.
La Thangue, N. B.
Cofactor strap regulates oxidative phosphorylation and mitochondrial p53 activity through ATP synthase
author_facet Maniam, Sandra
Coutts, Amanda S.
Stratford, Michael R. L.
McGouran, Joanna F.
Kessler, Benedikit M.
La Thangue, N. B.
author_sort Maniam, Sandra
title Cofactor strap regulates oxidative phosphorylation and mitochondrial p53 activity through ATP synthase
title_short Cofactor strap regulates oxidative phosphorylation and mitochondrial p53 activity through ATP synthase
title_full Cofactor strap regulates oxidative phosphorylation and mitochondrial p53 activity through ATP synthase
title_fullStr Cofactor strap regulates oxidative phosphorylation and mitochondrial p53 activity through ATP synthase
title_full_unstemmed Cofactor strap regulates oxidative phosphorylation and mitochondrial p53 activity through ATP synthase
title_sort cofactor strap regulates oxidative phosphorylation and mitochondrial p53 activity through atp synthase
publisher Nature Publishing Group
publishDate 2015
url http://psasir.upm.edu.my/id/eprint/44087/1/Cofactor%20strap%20regulates%20oxidative%20phosphorylation%20and%20mitochondrial%20p53%20activity%20through%20ATP%20synthase.pdf
http://psasir.upm.edu.my/id/eprint/44087/
https://www.nature.com/articles/cdd2014135
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score 13.211869

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