What is it about?

There is an absolute necessity for de novo synthesized L-Ser for embryonic viability and tissue growth.L-Serine (L-Ser) plays versatile roles in metabolism as a necessary precursor for the synthesis of various biomolecules such as proteins, other nonessential amino acids, membrane lipids, and nucleotides, all of which are important for cell proliferation.3-phosphoglycerate dehydrogenase (Phgdh) is the first enzyme of de novo ʟ-Ser synthetic pathway.

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Why is it important?

Reduced availability of L-Ser limits cell proliferation and leads to an adaptation to L-Ser deficient environment, the underlying molecular mechanism of which remain largely unexplored.


L-Ser deprivation led to diminished cell proliferation and the activation of p38 MAPK and stress-activated protein kinase/Jun amino-terminal kinase in mouse embryonic fibroblasts. The resultant L-Ser 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-Ser 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-Ser supply is limited, L-Ser synthesized de novo in proliferating cells serves as a metabolic gatekeeper to maintain cell survival and the functions necessary for executing cell cycle progression.

Momoko Hamano
Kyushu Kogyo Daigaku

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This page is a summary of: Adaptive response to l ‐serine deficiency is mediated by p38 MAPK activation via 1‐deoxysphinganine in normal fibroblasts, FEBS Open Bio, March 2016, Wiley,
DOI: 10.1002/2211-5463.12038.
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