TY - JOUR A1 - Galhuber, Markus A1 - Michenthaler, Helene A1 - Heininger, Christoph A1 - Reinisch, Isabel A1 - Nössing, Christoph A1 - Krstic, Jelena A1 - Kupper, Nadja A1 - Moyschewitz, Elisabeth A1 - Auer, Martina A1 - Heitzer, Ellen A1 - Ulz, Peter A1 - Birner-Gruenberger, Ruth A1 - Liesinger, Laura A1 - Lenihan-Geels, Georgia Ngawai A1 - Oster, Moritz A1 - Spreitzer, Emil A1 - Chiozzi, Riccardo Zenezini A1 - Schulz, Tim J. A1 - Schupp, Michael A1 - Madl, Tobias A1 - Heck, Albert J. R. A1 - Prokesch, Andreas T1 - Complementary omics strategies to dissect p53 signaling networks under nutrient stress JF - Cellular and molecular life sciences N2 - 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. KW - p53 signaling KW - Nutrient stress KW - Starvation KW - Interactome KW - p53 targets Y1 - 2022 U6 - https://doi.org/10.1007/s00018-022-04345-8 SN - 1420-682X SN - 1420-9071 VL - 79 IS - 6 PB - Springer Nature CY - Basel ER -