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.
Inoue
Tomomi
T
The University of Chicago, Department of Radiation and Cellular Oncology, 5841 S. Maryland Ave, MC1105, Room G-06, Chicago, IL 60637, USA.
Wu
Liqing
L
Stuart
Jeremy
J
Maki
Carl G
CG
D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D005047:Etoposide / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006801:Humans; D051379:Mice; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D018384:Oxidative Stress; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D011839:Radiation, Ionizing; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D000935:Antifungal Agents; D005231:Fatty Acids, Unsaturated; D009687:Nuclear Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D005047:Etoposide; C497206:MDM2 protein, human; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2; C038753:leptomycin B