SOCS1 regulates senescence and ferroptosis by modulating the expression of p53 target genes
| Autor: | Subburaj Ilangumaran, Mathieu Vernier, Emmanuelle Saint-Germain, Diwakar Bobbala, Gerardo Ferbeyre, Lian Mignacca |
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| Přispěvatelé: | Université de Montréal (UdeM) |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Senescence Aging senescence tumor suppressor [SDV]Life Sciences [q-bio] Context (language use) SLC7A11 medicine.disease_cause Cell Line law.invention Transcriptome suppressor of cytokine signaling 03 medical and health sciences Suppressor of Cytokine Signaling 1 Protein 0302 clinical medicine law Cell Line Tumor medicine Humans Cellular Senescence ComputingMilieux_MISCELLANEOUS STAT5 biology Suppressor of cytokine signaling 1 Cell Biology ferroptosis Cell biology 030104 developmental biology Gene Expression Regulation KAP1 030220 oncology & carcinogenesis biology.protein Suppressor Tumor Suppressor Protein p53 Carcinogenesis Research Paper |
| Zdroj: | Aging Aging, Impact Journals, 2017, 9 (10), pp.2137-2162. ⟨10.18632/aging.101306⟩ Aging (Albany NY) |
| ISSN: | 1945-4589 |
| DOI: | 10.18632/aging.101306 |
| Popis: | The mechanism by which p53 suppresses tumorigenesis remains poorly understood. In the context of aberrant activation of the JAK/STAT5 pathway, SOCS1 is required for p53 activation and the regulation of cellular senescence. In order to identify p53 target genes acting during the senescence response to oncogenic STAT5A, we characterized the transcriptome of STAT5A-expressing cells after SOCS1 inhibition. We identified a set of SOCS1-dependent p53 target genes that include several secreted proteins and genes regulating oxidative metabolism and ferroptosis. Exogenous SOCS1 was sufficient to regulate the expression of p53 target genes and sensitized cells to ferroptosis. This effect correlated with the ability of SOCS1 to reduce the expression of the cystine transporter SLC7A11 and the levels of glutathione. SOCS1 and SOCS1-dependent p53 target genes were induced during the senescence response to oncogenic STAT5A, RasV12 or the tumor suppressor PML. However, while SOCS1 sensitized cells to ferroptosis neither RasV12 nor STAT5A mimicked the effect. Intriguingly, PML turned cells highly resistant to ferroptosis. The results indicate different susceptibilities to ferroptosis in senescent cells depending on the trigger and suggest the possibility of killing senescent cells by inhibiting pathways that mediate ferroptosis resistance. |
| Databáze: | OpenAIRE |
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