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The p53 tumor suppressor plays a key role in maintaining cellular integrity. In response to diverse stress signals, p53 can trigger apoptosis to eliminate damaged cells or cell-cycle arrest to enable cells to cope with stress and survive. However, the transcriptional networks underlying p53 pro-survival function are incompletely understood. Here, we show that in oncogenic-Ras-expressing cells, p53 promotes oxidative phosphorylation (OXPHOS) and cell survival upon glucose starvation. Analysis of p53 transcriptional activation domain mutants reveals that these responses depend on p53 transactivation function. Using gene expression profiling and ChIP-seq analysis, we identify several p53-inducible fatty acid metabolism-related genes. One such gene, Acad11, encoding a protein involved in fatty acid oxidation, is required for efficient OXPHOS and cell survival upon glucose starvation. This study provides new mechanistic insight into the pro-survival function of p53 and suggests that targeting this pathway may provide a strategy for therapeutic intervention based on metabolic perturbation.

Original publication

DOI

10.1016/j.celrep.2015.01.043

Type

Journal article

Journal

Cell Rep

Publication Date

24/02/2015

Volume

10

Pages

1096 - 1109

Keywords

Acyl-CoA Dehydrogenase, Amino Acid Sequence, Amino Acid Substitution, Animals, Cell Line, Tumor, Cell Survival, Gene Regulatory Networks, Glucose, Humans, Mice, Mice, Nude, Molecular Sequence Data, Neoplasms, Oxidative Phosphorylation, Protein Structure, Tertiary, RNA Interference, Sequence Alignment, Stress, Physiological, Transcriptional Activation, Transplantation, Heterologous, Tumor Suppressor Protein p53