Ribosomal protein RPL22/eL22 regulates the cell cycle by acting as an inhibitor of the CDK4-cyclin D complex.
Neylen Del ToroAna Fernandez-RuizLian MignaccaPaloma KalegariMarie-Camille RowellSebastian IgelmannEmmanuelle Saint-GermainMehdi BenfdilStéphane Lopes-PacienciaLéa Brakier-GingrasVéronique BourdeauGerardo FerbeyreFrédéric LessardPublished in: Cell cycle (Georgetown, Tex.) (2019)
Senescence is a tumor suppressor program characterized by a stable growth arrest while maintaining cell viability. Senescence-associated ribogenesis defects (SARD) have been shown to regulate senescence through the ability of the ribosomal protein S14 (RPS14 or uS11) to bind and inhibit the cyclin-dependent kinase 4 (CDK4). Here we report another ribosomal protein that binds and inhibits CDK4 in senescent cells: L22 (RPL22 or eL22). Enforcing the expression of RPL22/eL22 is sufficient to induce an RB and p53-dependent cellular senescent phenotype in human fibroblasts. Mechanistically, RPL22/eL22 can interact with and inhibit CDK4-Cyclin D1 to decrease RB phosphorylation both in vitro and in cells. Briefly, we show that ribosome-free RPL22/eL22 causes a cell cycle arrest which could be relevant during situations of nucleolar stress such as cellular senescence or the response to cancer chemotherapy.
Keyphrases
- cell cycle
- cell cycle arrest
- endothelial cells
- cell death
- cell proliferation
- pi k akt
- dna damage
- induced apoptosis
- stress induced
- binding protein
- protein protein
- amino acid
- signaling pathway
- poor prognosis
- quality improvement
- radiation therapy
- squamous cell carcinoma
- squamous cell
- oxidative stress
- endoplasmic reticulum stress
- long non coding rna