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Fludarabine nucleoside induces accumulations of p53, p63 and p73 in the nuclei of human B-lymphoid cell lines, with cytosolic and mitochondrial increases in p53.
MedLine Citation:
PMID:  22641291     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
PURPOSE: Human Raji cells treated with fludarabine nucleoside (2-FaraA, 3 μM) undergo apoptosis with accumulation of p53 in the nuclei as multiple phosphorylated isoforms and C-terminal truncated derivatives. Changes induced by 2-FaraA in the levels of p53, p63 and p73 in the nuclear, cytosolic and mitochondrial fractions have been determined in 4 human B-lymphoid cell lines that are TP53-functional (Raji and IM9) and TP53-mutated (MEC1 and U266). EXPERIMENTAL DESIGN: The B-lymphoid cell lines were treated with 2-FaraA (3 μM, 24 h, 48 h) and viability determined. Protein extracts of sub-cellular fractions from 2-FaraA-treated cells were analysed by 1D and 2D electrophoresis, multiple phosphorylated isoforms and truncated derivatives were identified by Western blots for p53, p63 and p73. RESULTS: p53 and p63 were present in all 3 fractions, while p73 was only detected in nuclei. After treatment with 2-FaraA, nuclear p53, p63 and p73 accumulated as multiple phosphorylated isoforms and truncated derivatives. The association of p63 with mitochondria in human cells is novel. CONCLUSIONS AND CLINICAL RELEVANCE: Comprehensive information on the sub-cellular distributions and responses of p53, p63 and p73 to 2-FaraA provides additional insight into mechanisms for induction of apoptosis in the treatment of B-lymphoproliferative disorders with fludarabine.
Authors:
Juhura G Almazi; Swetlana Mactier; O Giles Best; Ben Crossett; Stephen P Mulligan; Richard I Christopherson
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-29
Journal Detail:
Title:  Proteomics. Clinical applications     Volume:  -     ISSN:  1862-8354     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-5-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101298608     Medline TA:  Proteomics Clin Appl     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Affiliation:
School of Molecular Bioscience, University of Sydney, Sydney, NSW 2006, Australia.
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