Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.


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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

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


  1. 1.

    Locasale, J. W. et al. Nat. Genet. 43, 869–874 (2011).

    CAS  Article  Google Scholar 

  2. 2.

    Possemato, R. et al. Nature 476, 346–350 (2011).

    CAS  Article  Google Scholar 

  3. 3.

    Yang, M. & Vousden, K. H. Nat. Rev. Cancer 16, 650–662 (2016).

    CAS  Article  Google Scholar 

  4. 4.

    Ngo, B. et al. Cancer Discov. 10, 1352–1373 (2020).

    CAS  Article  Google Scholar 

  5. 5.

    Chaneton, B. et al. Nature 491, 458–462 (2012).

    CAS  Article  Google Scholar 

  6. 6.

    Rinaldi, G. et al. Molec. Cell 81, 386–397 (2021).

    CAS  Article  Google Scholar 

  7. 7.

    Ma, C. et al. Nat. Metab. (2021).

  8. 8.

    Unterlass, J. E. et al. Oncotarget 8, 104478–104491 (2017).

    Article  Google Scholar 

  9. 9.

    Sullivan, M. R. et al. eLife 8, e44235 (2019).

    CAS  Article  Google Scholar 

Download references


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.

Author information



Corresponding author

Correspondence to Sarah-Maria Fendt.

Ethics declarations

Competing interests

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

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Annibali, D., Fendt, SM. Nuclear PHGDH protects cancer cells from nutrient stress. Nat Metab 3, 1284–1285 (2021).

Download citation


Quick links