Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Galhuber, M; Michenthaler, H; Heininger, C; Reinisch, I; Nössing, C; Krstic, J; Kupper, N; Moyschewitz, E; Auer, M; Heitzer, E; Ulz, P; Birner-Gruenberger, R; Liesinger, L; Lenihan-Geels, GN; Oster, M; Spreitzer, E; Zenezini, Chiozzi, R; Schulz, TJ; Schupp, M; Madl, T; Heck, AJR; Prokesch, A.
Complementary omics strategies to dissect p53 signaling networks under nutrient stress.
Cell Mol Life Sci. 2022; 79(6):326
Doi: 10.1007/s00018-022-04345-8
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- Führende Autor*innen der Med Uni Graz
- Galhuber Markus
- Prokesch Andreas
- Co-Autor*innen der Med Uni Graz
- Auer Martina
- Birner-Grünberger Ruth
- Heininger Christoph
- Heitzer Ellen
- Krstic Jelena
- Kupper Nadja Julia
- Liesinger Laura
- Madl Tobias
- Michenthaler Helene
- Moyschewitz Elisabeth
- Reinisch Isabel Nadine
- Spreitzer Emil
- Ulz Peter
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- Abstract:
- Signaling trough p53is 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Carcinoma, Hepatocellular - metabolism
- Cell Nucleus - metabolism
- Cytoplasm - metabolism
- Humans - administration & dosage
- Liver Neoplasms - metabolism
- Nutrients - administration & dosage
- Signal Transduction - physiology
- Tumor Suppressor Protein p53 - genetics, metabolism
- Find related publications in this database (Keywords)
- p53 signaling
- Nutrient stress
- Starvation
- Interactome
- p53 targets