Document Detail

Loss of E-cadherin-mediated cell-cell contacts activates a novel mechanism for up-regulation of the proto-oncogene c-Jun.
MedLine Citation:
PMID:  19193763     Owner:  NLM     Status:  MEDLINE    
Loss of E-cadherin-mediated cell-cell contacts can elicit a signaling pathway that leads to acquisition of an invasive phenotype. Here, we show that at the receiving end of this pathway is the proto-oncogene c-Jun, a member of the activator protein-1 family of transcription factors that play a key role in stimulation of cell proliferation and tumor promotion. Cell separation or abrogation of E-cadherin-mediated cell-cell contacts both cause a dramatic increase in accumulation of the c-Jun protein. Unlike growth factors that enhance the expression of c-Jun by activating the transcription of the c-jun gene, the cell contact-dependent increase in c-Jun accumulation is not accompanied by a corresponding increase in c-Jun mRNA or c-Jun protein stability but rather in the translatability of the c-Jun transcript. Consistently, the increase in c-Jun accumulation is not dependent on activation of the mitogen-activated protein kinase or beta-catenin pathways but is mediated by signals triggered by the restructured cytoskeleton. Depolymerization of the cytoskeleton can mimic the effect of cell separation and cause a dramatic increase in c-Jun accumulation, whereas Taxol inhibits the cell contact-dependent increase. This novel mechanism of c-Jun regulation seems to underlie the robust overexpression of c-Jun in tumor cells of patients with colon carcinoma.
Revital Knirsh; Iris Ben-Dror; Barbara Spangler; Gideon D Matthews; Silke Kuphal; Anja K Bosserhoff; Lily Vardimon
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-02-04
Journal Detail:
Title:  Molecular biology of the cell     Volume:  20     ISSN:  1939-4586     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-01     Completed Date:  2009-07-01     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2121-9     Citation Subset:  IM    
Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978 Tel Aviv, Israel.
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MeSH Terms
Cadherins / metabolism*
Cell Communication*
Cell Line
Cytoskeleton / metabolism
Mitogen-Activated Protein Kinases / metabolism
Protein Biosynthesis
Proto-Oncogene Proteins c-jun / genetics*,  metabolism
RNA, Messenger / genetics,  metabolism
Transcription, Genetic
Up-Regulation / genetics*
Reg. No./Substance:
0/Cadherins; 0/Proto-Oncogene Proteins c-jun; 0/RNA, Messenger; EC Protein Kinases

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