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Figure 7


Fig. 7. Nucleoplasmic mobilization of nucleostemin stabilizes MDM2 and promotes G2-M transition and cell survival. (A) In dividing interphase cells, nucleostemin is localized in the nucleolus (grey circle), whereas MDM2 resides in the nucleoplasm (yellow circle) and blocks the activities (red cross) of p53 by ubiquitylation (Ub) and transcriptional inhibition. (B) The nucleoli are disassembled when exposed to drugs that trigger nucleolar stress or GTP depletion. In the nucleostemin-enriched cells (left panel), nucleoplasmic translocation of nucleostemin inhibits p53 activity (red cross) by stabilizing MDM2 and by competing with L23 for MDM2 binding. In the nucleostemin-deficient cells (right panel), MDM2 is either sequestered in the nucleolus by L23 or degraded, leading to G2-M arrest and cell death. (C) Nucleolar disassembly during mitosis releases nucleostemin into the nucleoplasm or cytoplasm, allowing nucleostemin to bind and stabilize MDM2. Stabilized MDM2 inhibits p53 function and safeguards the proliferation and survival of continuously dividing cells. Mit, mitochondria; 26S, 26S proteasome.





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