Journal
CELLULAR SIGNALLING
Volume 18, Issue 11, Pages 1941-1946Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2006.02.014
Keywords
IKK; beta-catenin; Wnt; NF-kappa B; Siah-1
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Funding
- NCI NIH HHS [CA 100849] Funding Source: Medline
- NIDCR NIH HHS [DE 015973] Funding Source: Medline
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beta-catenin is a bi-functional protein. It is not only a major component of the cellular adhesion machinery, but is also a transcription co-activator of the Writ signaling pathway. The cytosolic levels of the beta-catenin protein, as well as its subcellular localization, are tightly regulated due to its oncogenic potentials. Two independent pathways are found to regulate beta-catenin. The canonical pathway is induced by the Axin/adenomatous polyposis coli (APC)/glycogen synthase kinase-3 (GSK-3 beta) complex which is dependent on GSK-3 beta phosphorylation. The non-canonical pathway is mediated by p53-induced Siah-1 which is GSK-3 beta phosphorylation-independent. Recently, several studies reported that I kappa B kinase alpha (IKK alpha) could stabilize beta-catenin and stimulate beta-catenin/T cell factor (Tcf)-dependent transcription. Here we report that IKKa could inhibit beta-catenin degradation mediated not only by the Axin/APC/GSK-3 beta complex, but also by the Siah-1 pathway. Consistently, we found that IKK alpha abolished the inhibition of beta-catenin/Tcf-dependent transcription by Siah-1. Furthermore, we found that IKK alpha interacted with beta-catenin and inhibited beta-catenin ubiquitination. Taken together, our results provide a new insight into IKK alpha-mediated beta-catenin stabilization. (c) 2006 Elsevier Inc. All rights reserved.
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