Fig. 2.

Role of nucleolus in controlling proliferation of cancer cells. ARF and NPM1 are key nucleolar proteins that regulate proliferation through tumor suppressor p53 and oncogene c-Myc. A The binding of ARF to MDM2 allows the complex to translocate to the nucleolus allowing for the activation of the p53 pathway. B Binding of NPM1 and nucleolar ARF acts as a checkpoint for ribosome biogenesis. C Binding of NPM1 to c-Myc regulates hyperproliferation and transformation. D Role of c-Myc is context dependent. An increase in nucleolar c-Myc causes the stabilization of ARF resulting in ULF binding to c-Myc leading to the activation of the p53 pathway