Document Detail


PRIMA-1 cytotoxicity correlates with nucleolar localization and degradation of mutant p53 in breast cancer cells.
MedLine Citation:
PMID:  20946886     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PRIMA-1 has been identified as a compound that restores the transactivation function to mutant p53 and induces apoptosis in cells expressing mutant p53. Studies on subcellular distribution of the mutant p53 protein upon treatment with PRIMA-1Met, a methylated form of PRIMA-1, have suggested that redistribution of mutant p53 to nucleoli may play a role in PRIMA-1 induced apoptosis. Here, we specifically investigated the influence of PRIMA-1 on cellular localization of mutated p53-R280K endogenously expressed in tumour cells. By using immunofluorescence staining, we found a strong nucleolar redistribution of mutant p53 following PRIMA-1 treatment. This subcellular localization was associated to p53 degradation via ubiquitylation. When cells were treated with adriamycin, neither nucleolar redistribution nor mutant p53 down modulation and degradation were observed. Interestingly, cells where p53-R280K was silenced were more sensitive to PRIMA-1 than the parental ones. These results indicate that in some cellular context, the cell sensitivity to PRIMA-1 could depend on the abolition of a gain-of-function activity of the mutated p53, through a protein degradation pathway specifically induced by this compound.
Authors:
Debora Russo; Laura Ottaggio; Ilaria Penna; Giorgia Foggetti; Gilberto Fronza; Alberto Inga; Paola Menichini
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-12
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  402     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-15     Completed Date:  2010-12-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  345-50     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Molecular Mutagenesis and DNA Repair Unit, Department of Epidemiology and Prevention, National Cancer Research Institute (IST), 16132 Genova, Italy.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology*
Aza Compounds / pharmacology*
Bicyclo Compounds, Heterocyclic / pharmacology*
Breast Neoplasms / metabolism*
Cell Line, Tumor
Cell Nucleus / metabolism*
Drug Resistance, Neoplasm*
Female
Humans
Mutation
Tumor Suppressor Protein p53 / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/2,2-bis(hydroxymethyl)-1-azabicyclo(2,2,2,)octan-3-one; 0/Antineoplastic Agents; 0/Aza Compounds; 0/Bicyclo Compounds, Heterocyclic; 0/Tumor Suppressor Protein p53

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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