Genotoxic Stress in Normal Wild-Type Cells (left side of figure) Leads to Cell Senescence and Apoptosis Through the Action of p53, Which is Increased by a Switch From Cap-Dependent to Internal Ribosome Entry Site (IRES)-Mediated Translation. In dyskerindeficient cells (right side of figure), p53 mRNA association with ribosomes is altered, blunting the p53 response and thereby allowing cell proliferation and propagation of potentially oncogenic mutations. Similar mechanisms of cancer predisposition may apply to other disorders of ribosome function, and this model system may provide a platform to test the benefit of agents that modulate translational control.

Genotoxic Stress in Normal Wild-Type Cells (left side of figure) Leads to Cell Senescence and Apoptosis Through the Action of p53, Which is Increased by a Switch From Cap-Dependent to Internal Ribosome Entry Site (IRES)-Mediated Translation. In dyskerindeficient cells (right side of figure), p53 mRNA association with ribosomes is altered, blunting the p53 response and thereby allowing cell proliferation and propagation of potentially oncogenic mutations. Similar mechanisms of cancer predisposition may apply to other disorders of ribosome function, and this model system may provide a platform to test the benefit of agents that modulate translational control.

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