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@ARTICLE{Jiang:292544,
author = {X. Jiang$^*$ and A. H. Baig$^*$ and G. Palazzo$^*$ and R.
Del Pizzo$^*$ and T. Bortecen$^*$ and S. Groessl$^*$ and E.
A. Zaal and C. C. Amaya Ramirez$^*$ and A. Kowar$^*$ and D.
Aviles-Huerta$^*$ and C. R. Berkers and W. Palm$^*$ and D.
Tschaharganeh$^*$ and J. Krijgsveld$^*$ and F.
Loayza-Puch$^*$},
title = {{P}53-dependent hypusination of e{IF}5{A} affects
mitochondrial translation and senescence immune
surveillance.},
journal = {Nature Communications},
volume = {15},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DKFZ-2024-01787},
pages = {7458},
year = {2024},
note = {#EA:B250#LA:B250#LA:B230#},
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.},
keywords = {Peptide Initiation Factors: metabolism / Peptide Initiation
Factors: genetics / Eukaryotic Translation Initiation Factor
5A / Cellular Senescence / Tumor Suppressor Protein p53:
metabolism / RNA-Binding Proteins: metabolism / RNA-Binding
Proteins: genetics / Humans / Protein Biosynthesis /
Mitochondria: metabolism / Animals / Mice / Immunologic
Surveillance / Polyamines: metabolism / Ribosomal Proteins:
metabolism / Ribosomal Proteins: genetics / Lysine:
metabolism / Lysine: analogs $\&$ derivatives / Peptide
Initiation Factors (NLM Chemicals) / Eukaryotic Translation
Initiation Factor 5A (NLM Chemicals) / Tumor Suppressor
Protein p53 (NLM Chemicals) / RNA-Binding Proteins (NLM
Chemicals) / Polyamines (NLM Chemicals) / Ribosomal Proteins
(NLM Chemicals) / hypusine (NLM Chemicals) / Lysine (NLM
Chemicals)},
cin = {B250 / B230 / A330 / F190},
ddc = {500},
cid = {I:(DE-He78)B250-20160331 / I:(DE-He78)B230-20160331 /
I:(DE-He78)A330-20160331 / I:(DE-He78)F190-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39198484},
pmc = {pmc:PMC11358140},
doi = {10.1038/s41467-024-51901-w},
url = {https://inrepo02.dkfz.de/record/292544},
}