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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2015
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| Online Access: | http://psasir.upm.edu.my/id/eprint/44087/1/Cofactor%20strap%20regulates%20oxidative%20phosphorylation%20and%20mitochondrial%20p53%20activity%20through%20ATP%20synthase.pdf |
| _version_ | 1796974466191851520 |
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| author | Maniam, Sandra Coutts, Amanda S. Stratford, Michael R. L. McGouran, Joanna F. Kessler, Benedikit M. La Thangue, N. B. |
| 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 |
| collection | UPM |
| 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. |
| first_indexed | 2024-03-06T08:57:29Z |
| format | Article |
| id | upm.eprints-44087 |
| institution | Universiti Putra Malaysia |
| language | English |
| last_indexed | 2024-03-06T08:57:29Z |
| publishDate | 2015 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | 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 |
| 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 |
| title | 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_short | 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 |
| url | http://psasir.upm.edu.my/id/eprint/44087/1/Cofactor%20strap%20regulates%20oxidative%20phosphorylation%20and%20mitochondrial%20p53%20activity%20through%20ATP%20synthase.pdf |
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