FIP200 inhibits β-catenin-mediated transcription by promoting APC-independent β-catenin ubiquitination

• Published in: Oncogene Vol. 32; no. 19; pp. 2421 - 2432
• Main Authors: Choi, J D, Ryu, M, Ae Park, M, Jeong, G, Lee, J-S
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.05.2013; Nature Publishing Group
• Subjects: 631/67; 631/80/474/582; 631/80/86; Adenomatous polyposis coli; Adenomatous Polyposis Coli - genetics; Adenomatous Polyposis Coli - metabolism; Adenomatous Polyposis Coli Protein - genetics; Adenomatous Polyposis Coli Protein - metabolism; Apoptosis; Autophagy; beta Catenin - antagonists & inhibitors; beta Catenin - genetics; beta Catenin - metabolism; Breast cancer; Cell adhesion; Cell Biology; Focal adhesion kinase; Gene Expression Regulation; Genetic aspects; Genetic transcription; Glycogen; Glycogen synthase kinase 3; HCT116 Cells; Health aspects; HEK293 Cells; Human Genetics; Humans; Internal Medicine; Kinases; Medicine; Medicine & Public Health; Oncogenes; Oncology; original-article; Physiological aspects; Polyposis coli; Proteasome Endopeptidase Complex - metabolism; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - metabolism; Signal Transduction; Transcription; Transcription, Genetic; Tumor suppression; Tumors; Ubiquitin; Ubiquitin-proteasome system; Ubiquitin-protein ligase; Ubiquitination; Wnt protein; β-Catenin; United States; FIP200; β-catenin; ubiquitination
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2012.262

Focal adhesion kinase-family-interacting protein of 200 kDa (FIP200) has been shown to regulate multiple cellular functions, including cell adhesion, autophagy, development and proliferation. Furthermore, FIP200 is considered to have tumor-suppressive activity, which may be correlated with its inactivation in human breast cancers, in addition to its role as an important signal transduction node. Herein, we report that FIP200 interacts with the oncoprotein β-catenin. Moreover, FIP200 promotes destabilization of wild-type β-catenin, but not a cancer-causing form of β-catenin, and as a result represses the β-catenin-mediated transcription. FIP200-induced degradation of β-catenin is independent of adenomatous polyposis coli (APC) of the well-established β-catenin destruction complex (glycogen synthase kinase-3β/axin/APC), in a component of β-catenin E3 ubiquitin ligase, β-TrCP-dependent manner. Thus, the APC-independent β-catenin degradation by FIP200 suggests a role for FIP200 in tumor suppression in the presence of APC dysfunction. These findings reveal a new and important function of FIP200 in regulation of the Wnt/β-catenin pathway.