Journal Article

DKFZ-2024-01787

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png P53-dependent hypusination of eIF5A affects mitochondrial translation and senescence immune surveillance.

Jiang, X. (First author)DKFZ* ; Baig, A. H. (First author)DKFZ* ; Palazzo, G.DKFZ* ; Del Pizzo, R.DKFZ* ; Bortecen, T.DKFZ* ; Groessl, S.DKFZ* ; Zaal, E. A. ; Amaya Ramirez, C. C.DKFZ* ; Kowar, A.DKFZ* ; Aviles-Huerta, D.DKFZ* ; Berkers, C. R. ; Palm, W.DKFZ* ; Tschaharganeh, D.DKFZ* ; Krijgsveld, J. (Last author)DKFZ* ; Loayza-Puch, F. (Last author)DKFZ*

2024
Nature Publishing Group UK [London]

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Please use a persistent id in citations: doi:10.1038/s41467-024-51901-w

Abstract: 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.

Keyword(s): Peptide Initiation Factors: metabolism (MeSH) ; Peptide Initiation Factors: genetics (MeSH) ; Eukaryotic Translation Initiation Factor 5A (MeSH) ; Cellular Senescence (MeSH) ; Tumor Suppressor Protein p53: metabolism (MeSH) ; RNA-Binding Proteins: metabolism (MeSH) ; RNA-Binding Proteins: genetics (MeSH) ; Humans (MeSH) ; Protein Biosynthesis (MeSH) ; Mitochondria: metabolism (MeSH) ; Animals (MeSH) ; Mice (MeSH) ; Immunologic Surveillance (MeSH) ; Polyamines: metabolism (MeSH) ; Ribosomal Proteins: metabolism (MeSH) ; Ribosomal Proteins: genetics (MeSH) ; Lysine: metabolism (MeSH) ; Lysine: analogs & derivatives (MeSH) ; Peptide Initiation Factors ; Eukaryotic Translation Initiation Factor 5A ; Tumor Suppressor Protein p53 ; RNA-Binding Proteins ; Polyamines ; Ribosomal Proteins ; hypusine ; Lysine

Note: #EA:B250#LA:B250#LA:B230#

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Contributing Institute(s):

1. B250 NWG Translationskontrolle und Stoffwechsel (B250)
2. B230 Proteomik von Stammzellen und Krebs (B230)
3. A330 NWG Signaltransduktion und Stoffwechsel der Zelle (A330)
4. NWG Cell Plasticity and Epigenetic Remodeling (F190)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2024

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