Control of p53 nuclear accumulation in stressed cells.

Wild-type p53 accumulates in the nucleus following stress. Current models suggest this nuclear accumulation involves phosphorylation at p53 N-terminal sites, and inhibition of murine double minute (MDM)2-dependent nuclear export. We monitored the effects of stress on MDM2-dependent nuclear export of wild-type p53 and a mutant lacking N-terminal phosphorylation sites. Etoposide and ionizing radiation inhibited nuclear export of wild-type p53 and the phosphor-mutant to comparable extents, indicating nuclear export inhibition does not require N-terminal phosphorylation. Cytoplasmic p53 accumulated in the nucleus of transfected cells treated with the nuclear export-inhibitor leptomycin B (LMB). Interestingly, LMB caused less p53 nuclear accumulation than stress treatment, suggesting stress-induced nuclear accumulation of p53 does not result solely from inhibited nuclear export.