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IκBβ ‐related proteins in normal and transformed colonic epithelial cells
Author(s) -
Inan Mehmet Sait,
Place Robert,
Tolmacheva Veronica,
Wang QianShu,
Hubbard Andrea K.,
Rosenberg Daniel W.,
Giardina Charles
Publication year - 2000
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/1098-2744(200009)29:1<25::aid-mc4>3.0.co;2-a
Subject(s) - biology , lamina propria , microbiology and biotechnology , transcription factor , epithelium , gene isoform , nf κb , cell culture , b cell , antibody , signal transduction , immunology , biochemistry , gene , genetics
The transcription factor nuclear factor‐κB (NF‐κB) regulates genes that can influence cell proliferation, apoptosis, and inflammatory responses. Since these events can contribute to carcinogenesis, we examined the expression of NF‐κB inhibitory proteins (IκBs) in normal and transformed colonic epithelial cells. Immunohistochemical analysis of the mouse colon revealed a high level of IκBβ expression in epithelial cells relative to the rest of the tissue, whereas IκBα was found primarily in cells of the lamina propria. Mouse colon tumors showed a similar cell‐specific staining pattern. Immunoblot analysis of IκBβ from mouse colonocytes and the human HT‐29 colon cancer cell line indicated that most of the IκBβ in these cells was similar to the C‐terminal–truncated IκBβ2 isoform. Cell fractionation studies were consistent with IκBβ being a major regulator of p65‐p50 NF‐κB complexes in HT‐29 cells. Interestingly, two larger proteins specifically recognized by IκBβ 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‐κB, and their levels changed during the transient interleukin‐1β activation of NF‐κB in HT‐29 cells. Evidence was obtained indicating that p106 and p112 are stably ubiquitinated forms of IκBβ. We propose that deficiencies in the proteasomal degradation of IκBβ lead to p106 and p112 accumulation, which in turn alter NF‐κB regulation in colon cancer cells. Mol. Carcinog. 29:25–36, 2000. © 2000 Wiley‐Liss, Inc.