Back to Search
Start Over
Analysis of p53 Transactivation Domain Mutants Reveals Acad11 as a Metabolic Target Important for p53 Pro-Survival Function
- Source :
- Cell Reports, Vol 10, Iss 7, Pp 1096-1109 (2015)
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
Abstract
- SummaryThe 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.
- Subjects :
- Transcriptional Activation
Cell Survival
Mutant
Molecular Sequence Data
Transplantation, Heterologous
Mice, Nude
Oxidative phosphorylation
Biology
General Biochemistry, Genetics and Molecular Biology
Acyl-CoA Dehydrogenase
Oxidative Phosphorylation
Article
Transactivation
Mice
RNA interference
Stress, Physiological
Cell Line, Tumor
Neoplasms
Animals
Humans
Gene Regulatory Networks
Amino Acid Sequence
Gene
lcsh:QH301-705.5
Protein Structure, Tertiary
Transplantation
Gene expression profiling
Glucose
Biochemistry
Amino Acid Substitution
lcsh:Biology (General)
Cell culture
RNA Interference
Tumor Suppressor Protein p53
Sequence Alignment
Subjects
Details
- ISSN :
- 22111247
- Volume :
- 10
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Cell Reports
- Accession number :
- edsair.doi.dedup.....754d3ff0a265ddc609792686ca32b189
- Full Text :
- https://doi.org/10.1016/j.celrep.2015.01.043