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Crossregulation of NF‐κB by the APC/GSK‐3β/β‐catenin pathway
Author(s) -
Deng Jiong,
Xia Weiya,
Miller Stephanie A.,
Wen Yong,
Wang HongYing,
Hung MienChie
Publication year - 2004
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/mc.10169
Subject(s) - gsk 3 , biology , catenin , adenomatous polyposis coli , wnt signaling pathway , nf κb , small interfering rna , glycogen synthase , beta catenin , signal transduction , nfkb1 , cancer research , microbiology and biotechnology , phosphorylation , transcription factor , rna , biochemistry , genetics , gene , colorectal cancer , cancer
Abstract Glycogen synthase kinase‐3β (GSK‐3β) and adenomatous polyposis coli (APC) play an important role in the regulation of β‐catenin. Inhibition of or defects in their functions can lead to activation of β‐catenin. β‐catenin has been recently found to interact with and inhibit nuclear factor kappa B (NF‐κB). However, the regulatory roles of GSK‐3β/APC on the NF‐κB signaling pathway are unknown because of their diverse effects. In this study, we investigated whether GSK‐3β/APC might regulate NF‐κB activity through β‐catenin. We found that inhibition of GSK‐3β suppressed NF‐κB activity, whereas reexpression of APC restored NF‐κB activity in APC mutated cells. The regulatory effects were through β‐catenin because depletion of β‐catenin with small interfering RNA (siRNA) in the same systems reversed the effects. The regulatory relationship was further supported by the analysis of primary breast tumor tissues in vivo in which NF‐κB target TRAF1 was inversely correlated with activated β‐catenin. Thus, APC/GSK‐3β, through β‐catenin, may crossregulate NF‐κB signaling pathway. © 2004 Wiley‐Liss, Inc.