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

Xiangli Jiang, Ali Hyder Baig, Giuliana Palazzo, Rossella Pizzo, Toman Bortecen, Sven Groessl, Esther A. Zaal, Cinthia Claudia Amaya Ramirez, Alexander Kowar, Daniela Aviles-Huerta, Celia R. Berkers, Wilhelm Palm, Darjus Tschaharganeh, Jeroen Krijgsveld and Fabricio Loayza-Puch ()
Additional contact information
Xiangli Jiang: German Cancer Research Center (DKFZ), Heidelberg, Germany
Ali Hyder Baig: German Cancer Research Center (DKFZ), Heidelberg, Germany
Giuliana Palazzo: German Cancer Research Center (DKFZ), Heidelberg, Germany
Rossella Pizzo: German Cancer Research Center (DKFZ), Heidelberg, Germany
Toman Bortecen: University of Heidelberg
Sven Groessl: University of Heidelberg
Esther A. Zaal: Utrecht University
Cinthia Claudia Amaya Ramirez: German Cancer Research Center (DKFZ), Heidelberg, Germany
Alexander Kowar: German Cancer Research Center (DKFZ), Heidelberg, Germany
Daniela Aviles-Huerta: German Cancer Research Center (DKFZ), Heidelberg, Germany
Celia R. Berkers: Utrecht University
Wilhelm Palm: German Cancer Research Center (DKFZ)
Darjus Tschaharganeh: German Cancer Research Center (DKFZ)
Jeroen Krijgsveld: German Cancer Research Center (DKFZ)
Fabricio Loayza-Puch: German Cancer Research Center (DKFZ), Heidelberg, Germany

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-51901-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51901-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-51901-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().