title: FIP200 inhibits β-catenin-mediated transcription by promoting APC-independent β-catenin ubiquitination.
abstract: 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.
authors: Department of Molecular Science and Technology, College of Natural Sciences, Ajou University, Suwon, Korea.
authors: J D
authors: JD
authors: Choi
authors: M
authors: M
authors: Ryu
authors: M
authors: M
authors: Ae Park
authors: G
authors: G
authors: Jeong
authors: J-S
authors: JS
authors: Lee
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics / Q000378:metabolism*; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism; D000071183:Autophagy-Related Proteins; D005786:Gene Expression Regulation; D045325:HCT116 Cells; D057809:HEK293 Cells; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic; D054875:Ubiquitination; D051176:beta Catenin / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D000071183:Autophagy-Related Proteins; C407704:RB1CC1 protein, human; D051176:beta Catenin; D011505:Protein-Tyrosine Kinases; D046988:Proteasome Endopeptidase Complex