Abstract
We have previously identified PRIMA-1, a low molecular weight compound that restores the transcriptional transactivation function to mutant p53 and induction of apoptosis. To explore the molecular mechanism for PRIMA-1-induced mutant p53-dependent apoptosis, we examined the intracellular distribution of mutant p53 upon treatment with PRIMA-1MET by immunofluorescence staining. We found that PRIMA-1MET induced nucleolar translocation of mutant p53 and the promyelocytic leukemia (PML) nuclear body-associated proteins PML, CBP and Hsp70. Levels of Hsp70 were significantly enhanced by PRIMA-1MET treatment. PRIMA-Dead, a compound structurally related to PRIMA-1 but unable to induce mutant p53-dependent apoptosis, failed to induce nucleolar translocation of mutant p53. Our results suggest that redistribution of mutant p53 to nucleoli plays a role in PRIMA-1-induced apoptosis.
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Acknowledgements
This work was supported by grants from Cancerfonden, the Karolinska Institute, the Ingabritt & Arne Lundberg Foundation, and the 6th EU framework program. The information in this document is provided as is and no guarantee or warranty is given that the information is fit for any particular purpose. The user thereof uses the information at its sole risk and liability. The community is not liable for any use that may be made of the information contained herein.
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Rökaeus, N., Klein, G., Wiman, K. et al. PRIMA-1MET induces nucleolar accumulation of mutant p53 and PML nuclear body-associated proteins. Oncogene 26, 982–992 (2007). https://doi.org/10.1038/sj.onc.1209858
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DOI: https://doi.org/10.1038/sj.onc.1209858
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