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Complementary Omics Strategies to Dissect p53 Signaling Networks Under Nutrient Stress
- Source :
- Cellular and Molecular Life Sciences, 79(6), 1. Birkhauser Verlag Basel
- Publication Year :
- 2022
- Publisher :
- Research Square Platform LLC, 2022.
-
Abstract
- Signaling trough p53 is a major cellular stress response mechanism and increases upon nutrient stresses such as starvation. Here, we show in a human hepatoma cell line that starvation leads to robust nuclear p53 stabilization. Using BioID, we determine the cytoplasmic p53 interaction network within the immediate-early starvation response and show that p53 is dissociated from several metabolic enzymes and the kinase PAK2 for which direct binding with the p53 DNA-binding domain was confirmed with NMR studies. Furthermore, proteomics after p53 immunoprecipitation (RIME) uncovered the nuclear interactome under prolonged starvation, where we confirmed the novel p53 interactors SORBS1 (insulin receptor signaling) and UGP2 (glycogen synthesis). Finally, transcriptomics after p53 re-expression revealed a distinct starvation-specific transcriptome response and suggested previously unknown nutrient-dependent p53 target genes. Together, our complementary approaches delineate several nodes of the p53 signaling cascade upon starvation, shedding new light on the mechanisms of p53 as nutrient stress sensor. Given the central role of p53 in cancer biology and the beneficial effects of fasting in cancer treatment, the identified interaction partners and networks could pinpoint novel pharmacologic targets to fine-tune p53 activity.
- Subjects :
- Cytoplasm
Interactome
Carcinoma, Hepatocellular
Immunoprecipitation
Biology
Proteomics
Transcriptome
Cellular and Molecular Neuroscience
Cellular stress response
p53 targets
Humans
Molecular Biology
Cell Nucleus
Pharmacology
Kinase
Liver Neoplasms
Nutrients
Cell Biology
Cell biology
p53 signaling
Insulin receptor
Nutrient stress
Starvation
biology.protein
Molecular Medicine
Tumor Suppressor Protein p53
Starvation response
Signal Transduction
Subjects
Details
- ISSN :
- 1420682X
- Database :
- OpenAIRE
- Journal :
- Cellular and Molecular Life Sciences, 79(6), 1. Birkhauser Verlag Basel
- Accession number :
- edsair.doi.dedup.....79044ec942b94d24bde502984b8220de