Fig. 5
From: Ribosomal proteins and human diseases: molecular mechanisms and targeted therapy
A model of the transition from cellular hypo-proliferation to hyper-proliferation in ribosomopathies. Defects in ribosome biogenesis and ribosome function induce p53 activation via the nucleolar stress response, but also activate the p53-independent DNA damage response (DDR). Defects in ribosome biogenesis also result in the selective translation of subsets of mRNAs involved in the regulation of cellular metabolism. In turn, deregulation of metabolism leads to oxidative stress that further impairs ribosome biogenesis and ribosome function. These nucleolar and metabolic stresses result in hypo-proliferative responses including cell cycle arrest, senescence or apoptosis that parallel the hypo-proliferative phenotypes associated with ribosomopathies. Chronic deregulation of ribosome biogenesis and cellular metabolism promotes genomic instability and secondary mutations, leading to the outgrowth of clones harboring translationally driven elevated metabolism and pro-survival mechanisms that underpin the transition from hypo-proliferation to hyper-proliferation phenotypes and cancer predisposition in ribosomopathies
