Document Detail


Overexpressed poly(ADP-ribose) polymerase delays the release of rat cells from p53-mediated G(1) checkpoint.
MedLine Citation:
PMID:  11029756     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have previously reported that in cells ectopically expressing temperature-sensitive p53(135val) mutant, p53 formed tight complexes with poly(ADP-ribose) polymerase (PARP). At elevated temperatures, p53(135val) protein, adopting the mutant phenotype, was localized in the cytoplasm and sequestered the endogenous PARP. To prove whether an excess of p53(135val) protein led to this unusual intracellular distribution of PARP, we have established cell lines overexpressing p53(135val) + c-Ha-ras alone or in combination with PARP. Interestingly, immunostaining revealed that PARP is sequestered in the cytoplasm by mutant p53 in cells overexpressing both proteins. Simultaneous overexpression of PARP had no effect on temperature-dependent cell proliferation and only negligibly affected the kinetics of p53-mediated G(1) arrest. However, if the cells were completely growth arrested at 32 degrees C and then shifted up to 37 degrees C, coexpressed PARP dramatically delayed the reentry of transformed cells into the cell cycle. Even after 72 h at 37 degrees C the proportion of S-phase cells was reduced to 20% compared to those expressing only p53(135val) + c-Ha-ras. The coexpressed PARP stabilized wt p53 protein and its enzymatic activity was necessary for stabilization.
Authors:
J Wesierska-Gadek; G Schmid
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  80     ISSN:  0730-2312     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2000 Sep 
Date Detail:
Created Date:  2000-12-04     Completed Date:  2000-12-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  85-103     Citation Subset:  IM    
Copyright Information:
Copyright 2000 Wiley-Liss, Inc.
Affiliation:
Institute of Cancer Research, University of Vienna, Borschkegasse 8 a, A-1090 Vienna, Austria. Jozefa.Antonia.Gadek-Wesierski@univie.ac.at
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Division / genetics
Cell Line, Transformed
Fluorescent Antibody Technique, Indirect
G1 Phase / genetics*
Phenotype
Poly(ADP-ribose) Polymerases / metabolism*
Precipitin Tests
Rats
Tumor Suppressor Protein p53 / genetics,  physiology*
Chemical
Reg. No./Substance:
0/Tumor Suppressor Protein p53; EC 2.4.2.30/Poly(ADP-ribose) Polymerases

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