P53-dependent hypusination of eIF5A affects mitochondrial translation and senescence immune surveillance.

Autor: Jiang X; Translational Control and Metabolism, German Cancer Research Center (DKFZ), Heidelberg, Germany, Heidelberg, Germany.; Department of Thoracic Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, China., Baig AH; Translational Control and Metabolism, German Cancer Research Center (DKFZ), Heidelberg, Germany, Heidelberg, Germany., Palazzo G; Translational Control and Metabolism, German Cancer Research Center (DKFZ), Heidelberg, Germany, Heidelberg, Germany.; Faculty of Biosciences, University of Heidelberg, Heidelberg, Germany., Del Pizzo R; Translational Control and Metabolism, German Cancer Research Center (DKFZ), Heidelberg, Germany, Heidelberg, Germany.; Faculty of Biosciences, University of Heidelberg, Heidelberg, Germany., Bortecen T; Faculty of Biosciences, University of Heidelberg, Heidelberg, Germany.; Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany., Groessl S; Faculty of Biosciences, University of Heidelberg, Heidelberg, Germany.; Division of Cell Signaling and Metabolism, German Cancer Research Center (DKFZ), Heidelberg, Germany., Zaal EA; Division of Cell Biology, Metabolism and Cancer, Department Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, CL, Utrecht, The Netherlands., Amaya Ramirez CC; Translational Control and Metabolism, German Cancer Research Center (DKFZ), Heidelberg, Germany, Heidelberg, Germany., Kowar A; Translational Control and Metabolism, German Cancer Research Center (DKFZ), Heidelberg, Germany, Heidelberg, Germany.; Faculty of Biosciences, University of Heidelberg, Heidelberg, Germany., Aviles-Huerta D; Translational Control and Metabolism, German Cancer Research Center (DKFZ), Heidelberg, Germany, Heidelberg, Germany.; Faculty of Biosciences, University of Heidelberg, Heidelberg, Germany., Berkers CR; Division of Cell Biology, Metabolism and Cancer, Department Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, CL, Utrecht, The Netherlands., Palm W; Division of Cell Signaling and Metabolism, German Cancer Research Center (DKFZ), Heidelberg, Germany., Tschaharganeh D; Cell Plasticity and Epigenetic Remodeling, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany., Krijgsveld J; Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Medical Faculty, University of Heidelberg, Heidelberg, Germany., Loayza-Puch F; Translational Control and Metabolism, German Cancer Research Center (DKFZ), Heidelberg, Germany, Heidelberg, Germany. f.loayza-puch@dkfz-heidelberg.de.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Aug 28; Vol. 15 (1), pp. 7458. Date of Electronic Publication: 2024 Aug 28.
DOI: 10.1038/s41467-024-51901-w
Abstrakt: Cellular senescence is characterized by a permanent growth arrest and is associated with tissue aging and cancer. Senescent cells secrete a number of different cytokines referred to as the senescence-associated secretory phenotype (SASP), which impacts the surrounding tissue and immune response. Here, we find that senescent cells exhibit higher rates of protein synthesis compared to proliferating cells and identify eIF5A as a crucial regulator of this process. Polyamine metabolism and hypusination of eIF5A play a pivotal role in sustaining elevated levels of protein synthesis in senescent cells. Mechanistically, we identify a p53-dependent program in senescent cells that maintains hypusination levels of eIF5A. Finally, we demonstrate that functional eIF5A is required for synthesizing mitochondrial ribosomal proteins and monitoring the immune clearance of premalignant senescent cells in vivo. Our findings establish an important role of protein synthesis during cellular senescence and suggest a link between eIF5A, polyamine metabolism, and senescence immune surveillance.
(© 2024. The Author(s).)
Databáze: MEDLINE
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