P53-mediated adaptation to serine starvation is retained by a common tumour-derived mutant.

ABSTRACT:

Background

In response to oncogenic stress, the tumour suppressor protein p53 can induce the elimination of cells through induction of cell death or senescence, helping to restrain malignant progression. Conversely, under nutrient stress, p53 can protect cells by supporting metabolic adaptation. Many cancers express mutant p53 proteins that have lost the cell-elimination properties of wild-type p53. However, a previous report showed that a tumour-derived mutant can retain the ability to support cells under glutamine starvation.

Results

We show that a commonly occurring p53 mutant, R248W, retains wild-type ability to support survival under serine starvation. R248W, but not R175H, can engage p21 and MDM2, which both function to limit oxidative stress and facilitate the switch

SUBMITTER: Humpton TJ 

PROVIDER: S-EPMC6276204 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature