Research ArticleMetabolism

p53 is regulated by aerobic glycolysis in cancer cells by the CtBP family of NADH-dependent transcriptional regulators

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Science Signaling  05 May 2020:
Vol. 13, Issue 630, eaau9529
DOI: 10.1126/scisignal.aau9529

Protective p53 response

To fuel their rapid proliferation, tumor cells increase their rates of glycolysis, which not only generates precursors for biosynthetic pathways but also results in an increase in the NADH:NAD+ ratio. Birts et al. found that, in highly glycolytic cancer cells in vitro, the increased NADH:NAD+ ratio resulted in an increase in the abundance of the NADH-bound forms of CtBP family transcriptional regulators, which prevented their interaction with the p53-binding protein HDM2, thus enabling the accumulation of p53. The resulting expression of p53 target genes was required to maintain metabolic homeostasis, highlighting a role for p53 in protecting cells from glycolytic stress.

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