Adenomatous polyposis coli (APC) differentially regulates β-catenin phosphorylation and ubiquitination in colon cancer cells

Jun Yang, Wen Zhang, Paul M. Evans, Xi Chen, Xi He, Chunming Liu

Research output: Contribution to journalArticle

137 Citations (Scopus)

Abstract

Most colorectal cancers have mutations of the adenomatous polyposis coli (APC) gene or the β-catenin gene that stabilize β-catenin and activate β-catenin target genes, leading ultimately to cancer. The molecular mechanisms of APC function in β-catenin degradation are not completely known. APC binds β-catenin and is involved in the Axin complex, suggesting that APC regulates β-catenin phosphorylation. Some evidence also suggests that APC regulates β-catenin nuclear export. Here, we examine the effects of APC mutations on β-catenin phosphorylation, ubiquitination, and degradation in the colon cancer cell lines SW480, DLD-1, and HT29, each of which contains a different APC truncation. Although the current models suggest that β-catenin phosphorylation should be inhibited by APC mutations, we detected significant β-catenin phosphorylation in these cells. However, β-catenin ubiquitination and degradation were inhibited in SW480 but not in DLD-1 and HT29 cells. The ubiquitination of β-catenin in SW480 cells can be rescued by exogenous expression of APC. The APC domains required for β-catenin ubiquitination were analyzed. Our results suggest that APC regulates β-catenin phosphorylation and ubiquitination by distinct domains and by separate molecular mechanisms.

Original languageEnglish (US)
Pages (from-to)17751-17757
Number of pages7
JournalJournal of Biological Chemistry
Volume281
Issue number26
DOIs
StatePublished - Jun 30 2006

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Catenins
Phosphorylation
Adenomatous Polyposis Coli
Ubiquitination
Colonic Neoplasms
Cells
Genes
Degradation
Mutation
APC Genes
HT29 Cells
Cell Nucleus Active Transport

ASJC Scopus subject areas

  • Biochemistry

Cite this

Adenomatous polyposis coli (APC) differentially regulates β-catenin phosphorylation and ubiquitination in colon cancer cells. / Yang, Jun; Zhang, Wen; Evans, Paul M.; Chen, Xi; He, Xi; Liu, Chunming.

In: Journal of Biological Chemistry, Vol. 281, No. 26, 30.06.2006, p. 17751-17757.

Research output: Contribution to journalArticle

Yang, Jun ; Zhang, Wen ; Evans, Paul M. ; Chen, Xi ; He, Xi ; Liu, Chunming. / Adenomatous polyposis coli (APC) differentially regulates β-catenin phosphorylation and ubiquitination in colon cancer cells. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 26. pp. 17751-17757.
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