Figures & data
Figure 1. Schematic representation of the ‘canonical' nucleolar stress response. Under normal growth conditions (left panel), the RPs are assembled with rRNAs into ribosomal subunits in the nucleolus and transported to the cytoplasm to form functional ribosomes. p53 activity is maintained at low levels by MDM2, via two mechanisms: i) MDM2 ubiquitinates p53 to promote its degradation; ii) the binding of MDM2 to p53 abrogates its interaction with Pol II transcription machinery. However in response to agents that induce nuclear stress like CX-5461 (right panel), the nucleolus is disrupted leading to the release of free RPs to the nucleoplasm where they bind MDM2 and prevent its interaction with p53 leading to increased p53 stability. The activation of p53 induces cell cycle arrest, apoptosis and/or senescence. Note additional molecules and mechanisms have been implicated in the nuclear stress response but are not shown for simplicity Citation[4-6].
![Figure 1. Schematic representation of the ‘canonical' nucleolar stress response. Under normal growth conditions (left panel), the RPs are assembled with rRNAs into ribosomal subunits in the nucleolus and transported to the cytoplasm to form functional ribosomes. p53 activity is maintained at low levels by MDM2, via two mechanisms: i) MDM2 ubiquitinates p53 to promote its degradation; ii) the binding of MDM2 to p53 abrogates its interaction with Pol II transcription machinery. However in response to agents that induce nuclear stress like CX-5461 (right panel), the nucleolus is disrupted leading to the release of free RPs to the nucleoplasm where they bind MDM2 and prevent its interaction with p53 leading to increased p53 stability. The activation of p53 induces cell cycle arrest, apoptosis and/or senescence. Note additional molecules and mechanisms have been implicated in the nuclear stress response but are not shown for simplicity Citation[4-6].](/cms/asset/5351c6a1-3635-4cf7-9ab3-b7915e04c919/iett_a_818658_f0001_b.jpg)
Table 1. Clinically approved drugs whose therapeutic effect is associated with disruption of ribosome biogenesis.