Direct ubiquitination of beta-catenin by Siah-1 and regulation by the exchange factor TBL1.

Dimitrova YN, Li J, Lee YT, Rios-Esteves J, Friedman DB, Choi HJ, Weis WI, Wang CY, Chazin WJ
J Biol Chem. 2010 285 (18): 13507-16

PMID: 20181957 · PMCID: PMC2859511 · DOI:10.1074/jbc.M109.049411

Beta-catenin is a key component of the Wnt signaling pathway that functions as a transcriptional co-activator of Wnt target genes. Upon UV-induced DNA damage, beta-catenin is recruited for polyubiquitination and subsequent proteasomal degradation by a unique, p53-induced SCF-like complex (SCF(TBL1)), comprised of Siah-1, Siah-1-interacting protein (SIP), Skp1, transducin beta-like 1 (TBL1), and adenomatous polyposis coli (APC). Given the complexity of the various factors involved and the novelty of ubiquitination of the non-phosphorylated beta-catenin substrate, we have investigated Siah-1-mediated ubiquitination of beta-catenin in vitro and in cells. Overexpression and purification protocols were developed for each of the SCF(TBL1) proteins, enabling a systematic analysis of beta-catenin ubiquitination using an in vitro ubiquitination assay. This study revealed that Siah-1 alone was able to polyubiquitinate beta-catenin. In addition, TBL1 was shown to play a role in protecting beta-catenin from Siah-1 ubiquitination in vitro and from Siah-1-targeted proteasomal degradation in cells. Siah-1 and TBL1 were found to bind to the same armadillo repeat domain of beta-catenin, suggesting that polyubiquitination of beta-catenin is regulated by competition between Siah-1 and TBL1 during Wnt signaling.

MeSH Terms (19)

Adaptor Proteins, Signal Transducing Adenomatous Polyposis Coli Protein Animals beta Catenin Calcium-Binding Proteins Cell-Free System Cell Line Humans Mice Nuclear Proteins Phosphoproteins Proteasome Endopeptidase Complex S-Phase Kinase-Associated Proteins Signal Transduction Transducin Tumor Suppressor Protein p53 Ubiquitin-Protein Ligases Ubiquitination Wnt Proteins

Connections (1)

This publication is referenced by other Labnodes entities:

Links