Document Detail


Inhibition of cell proliferation by the PCNA-binding region of p21 expressed as a GFP miniprotein.
MedLine Citation:
PMID:  11302688     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
p21 (WAF1/Cip1) is the only member of the CIP/KIP family which has a well-characterized PCNA-binding domain. p21 is known to have an important function in the coordination of the cellular pathways which are activated in response to DNA damage, though the significance of the p21-PCNA interaction is not completely clear. We have analyzed the effects of expressing a miniprotein containing the PCNA-binding domain of p21 upon the cell cycle and upon the proliferation of various cell types. We have compared this with the effect of expressing a mutant form which is defective in PCNA-binding, but which retains the secondary cyclin-CDK-inhibitory site. No PCNA-dependent effects were seen in the short term upon cell cycle distribution. However, clonogenic assays show that the GFP-peptide miniprotein can significantly suppress proliferation in a PCNA-dependent manner. In some cell types, however, the suppression of proliferation was not PCNA-dependent, suggesting that cellular environment is a contributory factor to the effect of this miniprotein. The capacity of this peptide sequence to suppress cell proliferation in vivo is of interest as the basis for the design of potential antiproliferative therapeutic agents.
Authors:
H Mattock; D P Lane; E Warbrick
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Experimental cell research     Volume:  265     ISSN:  0014-4827     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2001 May 
Date Detail:
Created Date:  2001-04-16     Completed Date:  2001-06-07     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  234-41     Citation Subset:  IM    
Copyright Information:
Copyright 2001 Academic Press.
Affiliation:
Department of Surgery and Molecular Oncology, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
Blotting, Western
Cell Division / genetics,  physiology*
Cyclin-Dependent Kinase Inhibitor p21
Cyclins / genetics,  metabolism*
Enzyme Inhibitors / metabolism*
Fluorescent Dyes / metabolism
Green Fluorescent Proteins
Humans
Luminescent Proteins / genetics,  metabolism
Microscopy, Fluorescence
Peptides / genetics,  metabolism*
Precipitin Tests
Proliferating Cell Nuclear Antigen / genetics,  metabolism*
Protein Structure, Tertiary
Recombinant Fusion Proteins / genetics,  metabolism
Transfection
Tumor Cells, Cultured
Tumor Stem Cell Assay
Chemical
Reg. No./Substance:
0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Enzyme Inhibitors; 0/Fluorescent Dyes; 0/Luminescent Proteins; 0/Peptides; 0/Proliferating Cell Nuclear Antigen; 0/Recombinant Fusion Proteins; 147336-22-9/Green Fluorescent Proteins

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


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