Control of p53 nuclear accumulation in stressed cells |
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Authors: | Inoue Tomomi Wu Liqing Stuart Jeremy Maki Carl G |
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Institution: | The University of Chicago, Department of Radiation and Cellular Oncology, 5841 S. Maryland Ave, MC1105, Room G-06, Chicago, IL 60637, USA. |
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Abstract: | 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. |
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Keywords: | MDM murine double minute NLS nuclear localization signal NES nuclear export signal IR ionizing radiation Etop etoposide Act D actinomycin D LMB leptomycin B HA hemagglutinin GFP green fluorescent protein OD oligomerization domain p53 N-Term a p53 mutant which lacks N-terminal phosphorylation sites S6 S9 S15 T18 S20 S33 and S37 |
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