β-catenin is a major transducer in Wnt signaling pathway, which is highly expressed in colorectal and other cancers. Previously, we have shown that β-catenin is down-regulated in colorectal cancer cells by glycoprotein, 90K, through ISGylation-dependent ubiquitination. The aim of this study is to further clarify a novel mechanism of β-catenin down-regulation pathway by 90K glycoprotein. To identify ISGylation site of β-catenin, deletion mutants of β-catenin lacking N- or C-terminal domain were employed. As only two lysine residues, K19 and K49, are reside in N-terminus of β-catenin, we sequenced cDNA of β- catenin from paired human colorectal cancer tissues to find the mutation and generated arginine point-mutation. As a result, there is no mutation on K19 and/or K49 in examined specimens and did not affect the 90K-mediated ISGylational degradation. To rule out the possibility of involving non-lysine residue in the ISG15 conjugation, such as serine or threonine, we constructed several deletion mutants and found that none are responsible for the ISG15 conjugation. Now, N-terminal portion of β-catenin is under screening for possible interactions with putative E3 ligases, and further detailed studies delineating the complex formation among ISG15 and β-catenin/E3 ligases are under way.

Citation Format: Somy Yoon, Jeong A Bae, Hangun Kim, Kyung-Sub Moon, Kyung Keun Kim. N-terminal portion of β-catenin is important in ISGylation of β-catenin by 90K glycoprotein in colorectal cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4431. doi:10.1158/1538-7445.AM2014-4431