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CANCER METABOLISM

Nuclear PHGDH protects cancer cells from nutrient stress

In this study, the serine biosynthetic enzyme PHGDH is shown to transition from the cytosol to the nucleus following nutrient stress. Nuclear PHGDH reduces local NAD+ availability needed for the PARylation of the transcription factor c-Jun. Consequently, c-Jun activity is reduced, contributing to sustained cancer cell proliferation.

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Fig. 1: Glucose deficiency induces alternative PHGDH activities in the nucleus.

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Acknowledgements

S.-M.F. acknowledges funding from the European Research Council under the ERC Consolidator Grant Agreement no. 771486–MetaRegulation, FWO Projects (G098120N, G088318N), Fonds Baillet Latour, KU Leuven-FTBO and the King Baudouin Foundation.

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Correspondence to Sarah-Maria Fendt.

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S.-M.F. has received funding from Bayer, Merck and BlackBelt Therapeutic and has consulted for Fund+. D.A. declares no competing interests.

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Annibali, D., Fendt, SM. Nuclear PHGDH protects cancer cells from nutrient stress. Nat Metab 3, 1284–1285 (2021). https://doi.org/10.1038/s42255-021-00448-x

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