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Sayano T, Kawano Y, Kusada W, et al. Adaptive response to l-serine deficiency is mediated by p38 MAPK activation via 1-deoxysphinganine in normal fibroblasts. FEBS Open Bio. 2016;6(4):303-16doi: 10.1002/2211-5463.12038.
Sayano, T., Kawano, Y., Kusada, W., Arimoto, Y., Esaki, K., Hamano, M., Udono, M., Katakura, Y., Ogawa, T., Kato, H., Hirabayashi, Y., & Furuya, S. (2016). Adaptive response to l-serine deficiency is mediated by p38 MAPK activation via 1-deoxysphinganine in normal fibroblasts. FEBS open bio, 6(4), 303-16. https://doi.org/10.1002/2211-5463.12038
Sayano, Tomoko, et al. "Adaptive response to l-serine deficiency is mediated by p38 MAPK activation via 1-deoxysphinganine in normal fibroblasts." FEBS open bio vol. 6,4 (2016): 303-16. doi: https://doi.org/10.1002/2211-5463.12038
Sayano T, Kawano Y, Kusada W, Arimoto Y, Esaki K, Hamano M, Udono M, Katakura Y, Ogawa T, Kato H, Hirabayashi Y, Furuya S. Adaptive response to l-serine deficiency is mediated by p38 MAPK activation via 1-deoxysphinganine in normal fibroblasts. FEBS Open Bio. 2016 Mar 03;6(4):303-16. doi: 10.1002/2211-5463.12038. eCollection 2016 Apr. PMID: 27239443; PMCID: PMC4821351.
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FEBS Open Bio. 2016 Mar 03;6(4):303-16. doi: 10.1002/2211-5463.12038. eCollection 2016 Apr.

Adaptive response to l-serine deficiency is mediated by p38 MAPK activation via 1-deoxysphinganine in normal fibroblasts.

FEBS open bio

Tomoko Sayano, Yuki Kawano, Wataru Kusada, Yashiho Arimoto, Kayoko Esaki, Momoko Hamano, Miyako Udono, Yoshinori Katakura, Takuya Ogawa, Hisanori Kato, Yoshio Hirabayashi, Shigeki Furuya

Affiliations

  1. Laboratory of Functional Genomics and Metabolism Department of Innovative Science and Technology for Bio-industry Graduate School of Bioresource and Bioenvironmental Sciences Kyushu University Fukuoka Japan; Laboratory for Molecular Membrane Neuroscience RIKEN Brain Science Institute Wako Saitama Japan.
  2. Department of Bioscience and Biotechnology Graduate School of Bioresource and Bioenvironmental Sciences Kyushu University Fukuoka Japan.
  3. Department of Genetic Resources Technology Graduate School of Bioresource and Bioenvironmental Sciences Kyushu University Fukuoka Japan.
  4. Department of Pharmaceutical Sciences International University of Health and Welfare Tochigi Japan.
  5. Corporate Sponsored Research Program 'Food for Life', Organization for Interdisciplinary Research Projects The University of Tokyo Japan.
  6. Laboratory for Molecular Membrane Neuroscience RIKEN Brain Science Institute Wako Saitama Japan.
  7. Laboratory of Functional Genomics and Metabolism Department of Innovative Science and Technology for Bio-industry Graduate School of Bioresource and Bioenvironmental Sciences Kyushu University Fukuoka Japan; Department of Bioscience and Biotechnology Graduate School of Bioresource and Bioenvironmental Sciences Kyushu University Fukuoka Japan; Department of Genetic Resources Technology Graduate School of Bioresource and Bioenvironmental Sciences Kyushu University Fukuoka Japan.

PMID: 27239443 PMCID: PMC4821351 DOI: 10.1002/2211-5463.12038

Abstract

UNLABELLED: Reduced availability of l-serine limits cell proliferation and leads to an adaptation to l-serine-deficient environment, the underlying molecular mechanism of which remain largely unexplored. Genetic ablation of 3-phosphoglycerate dehydrogenase (Phgdh), which catalyzes the first step of de novo l-serine synthesis, led to diminished cell proliferation and the activation of p38 MAPK and stress-activated protein kinase/Jun amino-terminal kinase in mouse embryonic fibroblasts under l-serine depletion. The resultant l-serine deficiency induced cyclin-dependent kinase inhibitor 1a (Cdkn1a; p21) expression, which was mediated by p38 MAPK. Survival of the Phgdh-deficient mouse embryonic fibroblasts was markedly reduced by p38 MAPK inhibition under l-serine depletion, whereas p38 MAPK could be activated by 1-deoxysphinganine, an atypical alanine-derived sphingoid base that was found to accumulate in l-serine-depleted mouse embryonic fibroblasts. These observations provide persuasive evidence that when the external l-serine supply is limited, l-serine synthesized de novo in proliferating cells serves as a metabolic gatekeeper to maintain cell survival and the functions necessary for executing cell cycle progression.

DATABASE: Gene Expression Omnibus, accession number GSE55687.

Keywords: cell proliferation; nutritional stress; p21; p38 MAPK; serine deficiency

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