title: GC-binding factor 2 interacts with dishevelled and regulates Wnt signaling pathways in human carcinoma cell lines.
abstract: GC-binding factor 2 (GCF2), a transcriptional repressor that decreases the activity of several genes is capable of binding directly to the GC-rich sequence of the EGFR promoter and repressing the transcriptional activity of EGFR. In addition to its function as a transcriptional repressor, GCF2 can directly interact with other proteins such as flightless-1 (Fli-1). Many previous findings pertaining to the function of Fli-1 have suggested a role for fli-1 in providing a direct link between molecules involved in signal transduction pathways and the actin cytoskeleton. We hypothesized that GCF2, together with Fli-1, plays a role in regulating cytoskeleton function, cell migration, and/or morphology. In our study, we observed that GCF2 is crucial for the activation of RhoA, a small GTPase that plays a key role in the regulation of the actin cytoskeleton. RhoA was markedly inactivated as a result of the decreased expression of GCF2. Co-immunoprecipitations were subsequently performed to further investigate the mechanism for the repressive function. We identified dishevelled (Dvl), which is the key mediator for the Wnt pathway, as a binding partner with GCF2. These results strongly suggest that GCF2 plays a role in the Wnt-noncanonical planar cell polarity (PCP) signaling pathway. Consequently, GCF2 may regulate the cytoskeleton or migration via Dvls and RhoA.
authors.affiliation: Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. ohtsuka@surg1.med.tohoku.ac.jp
authors.forename: Hideo
authors.initials: H
authors.lastname: Ohtsuka
authors.forename: Masaya
authors.initials: M
authors.lastname: Oikawa
authors.forename: Kyohei
authors.initials: K
authors.lastname: Ariake
authors.forename: Toshiki
authors.initials: T
authors.lastname: Rikiyama
authors.forename: Fuyuhiko
authors.initials: F
authors.lastname: Motoi
authors.forename: Yu
authors.initials: Y
authors.lastname: Katayose
authors.forename: Michiaki
authors.initials: M
authors.lastname: Unno
authors.forename: Alfred C
authors.initials: AC
authors.lastname: Johnson
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D045744:Cell Line, Tumor; D000072261:Dishevelled Proteins; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D051789:Proto-Oncogene Protein c-fli-1 / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D051153:Wnt Proteins / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; C078433:FLI1 protein, human; C114370:LRRFIP1 protein, human; D010750:Phosphoproteins; D051789:Proto-Oncogene Protein c-fli-1; D016601:RNA-Binding Proteins; D051153:Wnt Proteins; D020742:rhoA GTP-Binding Protein