Ribosomal stress: mechanisms and relevance to cancer

Protein translation is performed by ribosomes, complex macromolecular machines comprised of ribosomal proteins and ribosomal RNAs. Synthesis of ribosomes consumes around 60% of cell's energy and is rate-limiting step of cell growth and proliferation. Ribosome biogenesis is tightly linked with cell metabolism and cell cycle progression. Halt of the cell cycle due to activation of cell cycle checkpoints in response to DNA damage (DDR) is associated with inhibition of ribosomal DNA transcription, which is mediated by tumor suppressor p53. Conversely, unbalanced ribosomal biogenesis (ribosomal stress) is converted to p53-mediated inhibition of the cell cycle. Here we want to identify ribosomal proteins essential for p53 activation and their roles in DDR and to characterize the functional role of p53-regulated tumor suppressor PML in ribosomal stress in normal cells and how these processes are affected in tumor cells. Elucidating these mechanisms will help understand various human pathologies and may inspire new strategies to combat cancer.