Fig. 5.

Nucleolar factors in the activation of p53-dependent anticancer pathways. Stress factors in addition to nucleolar stress usually also elicit oxidative one. Nucleophosmin (NPM) seems to be a nucleolar molecule which initiates nucleolar response by recognizing nucleolar stress through oxidative stress. Then, other nucleolar factors such as nucleolin (NCL), ARF, 1A6/DRIM, Ltv1, or CSIG can block activity of Mdm2 which, under normal conditions, reduces p53 level preventing activation of p53-dependent pathways. Moreover, PICT-1-induced process of Mdm2 activity impairment is mediated by ribosomal proteins (RPs) both by RPs alone and in complex with 5S RNP. Mdm2 inhibition causes increase in p53 level, its stabilization, and activation of p53-mediated pathways leading cells to apoptosis, autophagy, senescence, metabolism change, and cell cycle arrest, or to DNA repair