Nucleolus Keeps p53 in Check

Science's STKE  18 Nov 2003:
Vol. 2003, Issue 209, pp. tw447-TW447
DOI: 10.1126/stke.2092003TW447

Nucleolar disruption may be the trigger for p53 stabilization and activation in response to diverse cellular stresses, report Rubbi and Milner. The stabilization and activation of p53 can lead to cell-cycle arrest or apoptosis and may contribute to DNA damage repair. Many p53-stimulating drugs or cellular stresses disrupt nucleolar function, which also varies with the cell cycle and, thus, provides a mechanism for cell cycle-dependent changes in p53 levels. Immunofluorescence analysis of cells exposed to p53-stabilizing treatments revealed a correlated increase in nucleolar stability, as measured by translocation of the nucleolar protein NPM to the nucleus. Micropore filters were used to deliver ultraviolet radiation to focused regions of the nucleus at doses that can trigger p53 response if applied to the whole nucleus. This focused irradiation did not cause nucleolar disruption and did not lead to increased abundance of p53. Direct disruption of the nucleolus by microinjection of antibodies against the nucleolar protein UBF stimulated p53 stabilization and the expression of the p53 target p21. Although UBF-mediated disruption of the nucleolus stimulated p53 phosphorylation, so did injection of control antibodies. Thus, phosphorylation did not appear to be required for p53 stabilization. The authors suggest that the p53 response must be prevented by degradation promoted by a functional nucleolus.

C. P. Rubbi, J. Milner, Disruption of the nucleolus mediates stabilization of p53 in response to DNA damage and other stresses. EMBO J. 22, 6068-6077 (2003). [Abstract] [Full Text]