Document Detail


Estrogen receptor protects p53 from deactivation by human double minute-2.
MedLine Citation:
PMID:  10766163     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We and others have demonstrated that estrogen receptor alpha (ERalpha) and p53, two important regulatory proteins in breast cancer, bind to each other. In this report, using the glutathione S-transferase pull-down methodology, we show the ligand-independent interaction of ERalpha with the NH2-terminal region of p53, a region known to bind the p300 and human double minute-2 (hdm2) regulatory factors. Furthermore, we have demonstrated that ERalpha is capable of binding hdm2 directly. The interaction of ERalpha and p53 does not interfere with the binding between p53 and hdm2; rather, these proteins form a ternary complex. The effect of ERalpha on the p53-hdm2 regulatory loop has been examined. Our results indicate that ERalpha protects p53 from being deactivated by hdm2. It is evident from these investigations that the ligand-independent protection of p53 by ERalpha is a novel role for this protein in addition to its classic regulatory function as a ligand-inducible transcription factor. This study also describes a new mechanism of cellular regulation of p53 activity.
Authors:
G Liu; J A Schwartz; S C Brooks
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer research     Volume:  60     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  2000 Apr 
Date Detail:
Created Date:  2000-05-04     Completed Date:  2000-05-04     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1810-4     Citation Subset:  IM    
Affiliation:
Graduate Program in Cancer Biology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
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MeSH Terms
Descriptor/Qualifier:
Breast Neoplasms
Estrogen Receptor alpha
Female
Glutathione Transferase / genetics
Hela Cells
Humans
Neoplasm Proteins / metabolism
Nuclear Proteins*
Polymerase Chain Reaction
Protein Biosynthesis
Proto-Oncogene Proteins / metabolism*
Proto-Oncogene Proteins c-mdm2
Receptors, Estrogen / metabolism*
Recombinant Fusion Proteins / metabolism
Transfection
Tumor Cells, Cultured
Tumor Suppressor Protein p53 / metabolism*
Grant Support
ID/Acronym/Agency:
CA 68655/CA/NCI NIH HHS; DK 54837/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Estrogen Receptor alpha; 0/Neoplasm Proteins; 0/Nuclear Proteins; 0/Proto-Oncogene Proteins; 0/Receptors, Estrogen; 0/Recombinant Fusion Proteins; 0/Tumor Suppressor Protein p53; EC 2.5.1.18/Glutathione Transferase; EC 6.3.2.19/MDM2 protein, human; EC 6.3.2.19/Proto-Oncogene Proteins c-mdm2

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


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