Document Detail

Anoikis triggers Mdm2-dependent p53 degradation.
MedLine Citation:
PMID:  20577896     Owner:  NLM     Status:  MEDLINE    
The extracellular matrix (ECM) plays a key role in cell-cell communication and signaling, and the signals it propagates are important for tissue remodeling and survival. However, signals from disease-altered ECM may lead to anoikis-apoptotic cell death triggered by loss of ECM contacts. Previously, we found that an altered fibronectin matrix triggers anoikis in human primary ligament cells via a pathway that requires p53 transcriptional downregulation. Here we show that this p53 reduction is suppressed by transfecting cells with Mdm2 antisense oligonucleotides or small interfering RNA. Similar results were found in cells treated to prevent p53 and Mdm2 interactions. When p53 was overexpressed in cells lacking Mdm2 and p53, p53 levels were unaffected by anoikis conditions. However, cells cotransfected with p53 and wild type Mdm2, but not a mutant Mdm2, exhibited decreased p53 levels in response to anoikis conditions. Thus, cells under anoikis conditions undergo p53 degradation that is mediated by Mdm2.
Abhijit Ghosh; Tina Chunyuan Chen; Yvonne L Kapila
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-06-26
Journal Detail:
Title:  Molecular and cellular biochemistry     Volume:  343     ISSN:  1573-4919     ISO Abbreviation:  Mol. Cell. Biochem.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-21     Completed Date:  2011-03-01     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  0364456     Medline TA:  Mol Cell Biochem     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  201-9     Citation Subset:  IM    
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MeSH Terms
Blotting, Western
Enzyme-Linked Immunosorbent Assay
Proto-Oncogene Proteins c-mdm2 / physiology*
Tumor Suppressor Protein p53 / metabolism*
Grant Support
Reg. No./Substance:
0/Tumor Suppressor Protein p53; EC protein, human; EC Proteins c-mdm2

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