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Phosphoglycerate dehydrogenase activates PKM2 to phosphorylate histone H3T11 and attenuate cellular senescence
Vascular endothelial cells (ECs) senescence correlates with the increase of cardiovascular diseases in ageing population. Although ECs rely on glycolysis for energy production, little is known about the role of glycolysis in ECs senescence. Here, we report a critical role for glycolysis-derived seri...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10006232/ https://www.ncbi.nlm.nih.gov/pubmed/36899022 http://dx.doi.org/10.1038/s41467-023-37094-8 |
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author | Wu, Yinsheng Tang, Lixu Huang, Han Yu, Qi Hu, Bicheng Wang, Gang Ge, Feng Yin, Tailang Li, Shanshan Yu, Xilan |
author_facet | Wu, Yinsheng Tang, Lixu Huang, Han Yu, Qi Hu, Bicheng Wang, Gang Ge, Feng Yin, Tailang Li, Shanshan Yu, Xilan |
author_sort | Wu, Yinsheng |
collection | PubMed |
description | Vascular endothelial cells (ECs) senescence correlates with the increase of cardiovascular diseases in ageing population. Although ECs rely on glycolysis for energy production, little is known about the role of glycolysis in ECs senescence. Here, we report a critical role for glycolysis-derived serine biosynthesis in preventing ECs senescence. During senescence, the expression of serine biosynthetic enzyme PHGDH is significantly reduced due to decreased transcription of the activating transcription factor ATF4, which leads to reduction of intracellular serine. PHGDH prevents premature senescence primarily by enhancing the stability and activity of pyruvate kinase M2 (PKM2). Mechanistically, PHGDH interacts with PKM2, which prevents PCAF-catalyzed PKM2 K305 acetylation and subsequent degradation by autophagy. In addition, PHGDH facilitates p300-catalyzed PKM2 K433 acetylation, which promotes PKM2 nuclear translocation and stimulates its activity to phosphorylate H3T11 and regulate the transcription of senescence-associated genes. Vascular endothelium-targeted expression of PHGDH and PKM2 ameliorates ageing in mice. Our findings reveal that enhancing serine biosynthesis could become a therapy to promote healthy ageing. |
format | Online Article Text |
id | pubmed-10006232 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-100062322023-03-12 Phosphoglycerate dehydrogenase activates PKM2 to phosphorylate histone H3T11 and attenuate cellular senescence Wu, Yinsheng Tang, Lixu Huang, Han Yu, Qi Hu, Bicheng Wang, Gang Ge, Feng Yin, Tailang Li, Shanshan Yu, Xilan Nat Commun Article Vascular endothelial cells (ECs) senescence correlates with the increase of cardiovascular diseases in ageing population. Although ECs rely on glycolysis for energy production, little is known about the role of glycolysis in ECs senescence. Here, we report a critical role for glycolysis-derived serine biosynthesis in preventing ECs senescence. During senescence, the expression of serine biosynthetic enzyme PHGDH is significantly reduced due to decreased transcription of the activating transcription factor ATF4, which leads to reduction of intracellular serine. PHGDH prevents premature senescence primarily by enhancing the stability and activity of pyruvate kinase M2 (PKM2). Mechanistically, PHGDH interacts with PKM2, which prevents PCAF-catalyzed PKM2 K305 acetylation and subsequent degradation by autophagy. In addition, PHGDH facilitates p300-catalyzed PKM2 K433 acetylation, which promotes PKM2 nuclear translocation and stimulates its activity to phosphorylate H3T11 and regulate the transcription of senescence-associated genes. Vascular endothelium-targeted expression of PHGDH and PKM2 ameliorates ageing in mice. Our findings reveal that enhancing serine biosynthesis could become a therapy to promote healthy ageing. Nature Publishing Group UK 2023-03-10 /pmc/articles/PMC10006232/ /pubmed/36899022 http://dx.doi.org/10.1038/s41467-023-37094-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Wu, Yinsheng Tang, Lixu Huang, Han Yu, Qi Hu, Bicheng Wang, Gang Ge, Feng Yin, Tailang Li, Shanshan Yu, Xilan Phosphoglycerate dehydrogenase activates PKM2 to phosphorylate histone H3T11 and attenuate cellular senescence |
title | Phosphoglycerate dehydrogenase activates PKM2 to phosphorylate histone H3T11 and attenuate cellular senescence |
title_full | Phosphoglycerate dehydrogenase activates PKM2 to phosphorylate histone H3T11 and attenuate cellular senescence |
title_fullStr | Phosphoglycerate dehydrogenase activates PKM2 to phosphorylate histone H3T11 and attenuate cellular senescence |
title_full_unstemmed | Phosphoglycerate dehydrogenase activates PKM2 to phosphorylate histone H3T11 and attenuate cellular senescence |
title_short | Phosphoglycerate dehydrogenase activates PKM2 to phosphorylate histone H3T11 and attenuate cellular senescence |
title_sort | phosphoglycerate dehydrogenase activates pkm2 to phosphorylate histone h3t11 and attenuate cellular senescence |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10006232/ https://www.ncbi.nlm.nih.gov/pubmed/36899022 http://dx.doi.org/10.1038/s41467-023-37094-8 |
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