TY  - JOUR
AU  - Jiang, Xiangli
AU  - Baig, Ali Hyder
AU  - Palazzo, Giuliana
AU  - Del Pizzo, Rossella
AU  - Bortecen, Toman
AU  - Groessl, Sven
AU  - Zaal, Esther A
AU  - Amaya Ramirez, Cinthia Claudia
AU  - Kowar, Alexander
AU  - Aviles-Huerta, Daniela
AU  - Berkers, Celia R
AU  - Palm, Wilhelm
AU  - Tschaharganeh, Darjus
AU  - Krijgsveld, Jeroen
AU  - Loayza-Puch, Fabricio
TI  - P53-dependent hypusination of eIF5A affects mitochondrial translation and senescence immune surveillance.
JO  - Nature Communications
VL  - 15
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DKFZ-2024-01787
SP  - 7458
PY  - 2024
N1  - #EA:B250#LA:B250#LA:B230#
AB  - 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.
KW  - Peptide Initiation Factors: metabolism
KW  - Peptide Initiation Factors: genetics
KW  - Eukaryotic Translation Initiation Factor 5A
KW  - Cellular Senescence
KW  - Tumor Suppressor Protein p53: metabolism
KW  - RNA-Binding Proteins: metabolism
KW  - RNA-Binding Proteins: genetics
KW  - Humans
KW  - Protein Biosynthesis
KW  - Mitochondria: metabolism
KW  - Animals
KW  - Mice
KW  - Immunologic Surveillance
KW  - Polyamines: metabolism
KW  - Ribosomal Proteins: metabolism
KW  - Ribosomal Proteins: genetics
KW  - Lysine: metabolism
KW  - Lysine: analogs & derivatives
KW  - Peptide Initiation Factors (NLM Chemicals)
KW  - Eukaryotic Translation Initiation Factor 5A (NLM Chemicals)
KW  - Tumor Suppressor Protein p53 (NLM Chemicals)
KW  - RNA-Binding Proteins (NLM Chemicals)
KW  - Polyamines (NLM Chemicals)
KW  - Ribosomal Proteins (NLM Chemicals)
KW  - hypusine (NLM Chemicals)
KW  - Lysine (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39198484
C2  - pmc:PMC11358140
DO  - DOI:10.1038/s41467-024-51901-w
UR  - https://inrepo02.dkfz.de/record/292544
ER  -