In colorectal cancer cells, APC, a tumor suppressor protein, is commonly expressed in truncated form. Truncation of APC is believed to disrupt degradation of xcexb2-catenin, which is regulated by a multiprotein complex called the destruction complex. The destruction complex comprises APC, Axin, xcexb2-catenin, serine/threonine kinases, and other proteins. The kinases CK1xcexb1 and GSK -3xcexb2, which are recruited by Axin, mediate phosphorylation of xcexb2-catenin, which initiates its ubiquitination and proteosomal degradation. The mechanism of regulation of xcexb2-catenin degradation by the destruction complex and the role of truncation of APC in colorectal cancer are not entirely understood. Through formulation and analysis of a rule-based computational model, we investigated the regulation of xcexb2-catenin phosphorylation and degradation by APC and the effect of APC truncation on function of the destruction complex. The model integrates available mechanistic knowledge about site-specific interactions and phosphorylation of destruction complex components and is consistent with an array of published data. We find that the phosphorylated truncated form of APC can outcompete Axin for binding to xcexb2-catenin, provided that Axin is limiting, and thereby sequester xcexb2-catenin away from Axin and the Axin-recruited kinases CK1xcexb1 and GSK -3xcexb2. Full-length APC also competes with Axin for binding to xcexb2-catenin, however, full-length APC is able, through its SAMP repeats, which bind Axin and which are missing in truncated oncogenic forms of APC, to bring xcexb2-catenin into indirect association with Axin and Axin-recruited kinases. Because our model indicates that the positive effects of truncated APC on xcexb2-catenin levels depend on phosphorylation of APC, at the first 20-amino acid repeat, and because phosphorylation of this site is mediated by CK1xcexb5, we suggest that CK1xcexb5 is a potential target for therapeutic intervention in colorectal cancer. Specific inhibition of CK1xcexb5 is predicted to limit binding of xcexb2-catenin to truncated APC and thereby to reverse the effect of APC truncation.