| Added by | lklinares |
|---|---|
| Group name | EquipeLL |
| Item Type | Journal Article |
| Title | Chromatin-Bound MDM2 Regulates Serine Metabolism and Redox Homeostasis Independently of p53 |
| Creator | Riscal et al. |
| Author | Romain Riscal |
| Author | Emilie Schrepfer |
| Author | Giuseppe Arena |
| Author | Madi Y. Cissé |
| Author | Floriant Bellvert |
| Author | Maud Heuillet |
| Author | Florian Rambow |
| Author | Eric Bonneil |
| Author | Frédérique Sabourdy |
| Author | Charles Vincent |
| Author | Thierry Levade |
| Author | Pierre Thibaut |
| Author | Jean-Christophe Marine |
| Author | Jean-Charles Portais |
| Author | Jean-Emmanuel Sarry |
| Author | Laurent Le Cam |
| Author | Laetitia K. Linares |
| Abstract | The mouse double minute 2 (MDM2) oncoprotein is recognized as a major negative regulator of the p53 tumor suppressor, but growing evidence indicates that its oncogenic activities extend beyond p53. Here, we show that MDM2 is recruited to chromatin independently of p53 to regulate a transcriptional program implicated in amino acid metabolism and redox homeostasis. Identification of MDM2 target genes at the whole-genome level highlights an important role for ATF3/4 transcription factors in tethering MDM2 to chromatin. MDM2 recruitment to chromatin is a tightly regulated process that occurs during oxidative stress and serine/glycine deprivation and is modulated by the pyruvate kinase M2 (PKM2) metabolic enzyme. Depletion of endogenous MDM2 in p53-deficient cells impairs serine/glycine metabolism, the NAD(+)/NADH ratio, and glutathione (GSH) recycling, impacting their redox state and tumorigenic potential. Collectively, our data illustrate a previously unsuspected function of chromatin-bound MDM2 in cancer cell metabolism. |
| Publication | Molecular Cell |
| Volume | 62 |
| Issue | 6 |
| Pages | 890-902 |
| Date | 06 16, 2016 |
| Journal Abbr | Mol Cell |
| Language | eng |
| DOI | 10.1016/j.molcel.2016.04.033 |
| ISSN | 1097-4164 |
| Library Catalog | PubMed |
| Extra | PMID: 27264869 |
| Tags | Activating Transcription Factor 4, Animals, Carcinoma, Non-Small-Cell Lung, Carrier Proteins, Cell Proliferation, Chromatin, Chromatin Assembly and Disassembly, Colonic Neoplasms, corresponding, first, Gene Expression Regulation, Neoplastic, Glycine, HCT116 Cells, Homeostasis, Humans, inca, last, ligue, Lung Neoplasms, Membrane Proteins, Mice, Nude, Mutation, original, Oxidation-Reduction, Oxidative Stress, Phosphorylation, Protein Binding, Proto-Oncogene Proteins c-mdm2, RNA Interference, Serine, Thyroid Hormones, Time Factors, top, Transcription, Genetic, Transfection, Tumor Burden, Tumor Suppressor Protein p53 |
| Date Added | 2024/12/03 - 09:12:56 |
| Date Modified | 2024/12/03 - 09:12:56 |
| Notes and Attachments | PubMed entry (Attachment) Texte intégral (Attachment) |
Institut de Recherche en Cancérologie de
