Document Detail

IkappaBbeta-related proteins in normal and transformed colonic epithelial cells.
MedLine Citation:
PMID:  11020244     Owner:  NLM     Status:  MEDLINE    
The transcription factor nuclear factor-kappaB (NF-kappaB) regulates genes that can influence cell proliferation, apoptosis, and inflammatory responses. Since these events can contribute to carcinogenesis, we examined the expression of NF-kappaB inhibitory proteins (IkappaBs) in normal and transformed colonic epithelial cells. Immunohistochemical analysis of the mouse colon revealed a high level of IkappaBbeta expression in epithelial cells relative to the rest of the tissue, whereas IkappaBalpha was found primarily in cells of the lamina propria. Mouse colon tumors showed a similar cell-specific staining pattern. Immunoblot analysis of IkappaBbeta from mouse colonocytes and the human HT-29 colon cancer cell line indicated that most of the IkappaBbeta in these cells was similar to the C-terminal-truncated IkappaBbeta2 isoform. Cell fractionation studies were consistent with IkappaBbeta being a major regulator of p65-p50 NF-kappaB complexes in HT-29 cells. Interestingly, two larger proteins specifically recognized by IkappaBbeta antibodies (p106 and p112) were found in HT-29 cells and in colon tissue of carcinogen-exposed mice. The p106 and p112 proteins bound to NF-kappaB, and their levels changed during the transient interleukin-1beta activation of NF-kappaB in HT-29 cells. Evidence was obtained indicating that p106 and p112 are stably ubiquitinated forms of IkappaBbeta. We propose that deficiencies in the proteasomal degradation of IkappaBbeta lead to p106 and p112 accumulation, which in turn alter NF-kappaB regulation in colon cancer cells.
M S Inan; R Place; V Tolmacheva; Q S Wang; A K Hubbard; D W Rosenberg; C Giardina
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular carcinogenesis     Volume:  29     ISSN:  0899-1987     ISO Abbreviation:  Mol. Carcinog.     Publication Date:  2000 Sep 
Date Detail:
Created Date:  2000-10-26     Completed Date:  2000-10-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8811105     Medline TA:  Mol Carcinog     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  25-36     Citation Subset:  IM    
Department of Molecular and Cell Biology, University of Connecticut, Storrs, Connecticut 06269-3125, USA.
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MeSH Terms
Cell Line, Transformed*
Colon / metabolism*
DNA-Binding Proteins / metabolism*
Epithelial Cells / metabolism
HT29 Cells
I-kappa B Proteins*
Reg. No./Substance:
0/DNA-Binding Proteins; 0/I kappa B beta protein; 0/I-kappa B Proteins

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