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Ribosome Biogenesis Stress and p53 Regulation

Impairment of ribosome biogenesis can result in quantitative or qualitative defects in protein synthesis and consequently lead to improper execution of the genetic program and the development of specific diseases. Evidence has accumulated over the last decade suggesting that perturbation of ribosome biogenesis triggers a p53-activating checkpoint signaling pathway trough inhibitory interactions of ribosomal proteins L5 and L11 with the p53 negative regulator, Mdm2. It was originally suggested that this pathway has a prominent role in preventing diseases by monitoring the fidelity of ribosome biogenesis. However, recent evidence suggests that p53 activation upon impairment of ribosome biogenesis might also be responsible for specific pathological manifestations in mammals. Our laboratory is focused on trying to understand the molecular basis of this checkpoint response and determining its role in pathogenesis of various diseases, including developmental abnormalities and cancer.

ribosome biogenesis; p53; cancer

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