Reference - Detail
|Author||Sato S, Idogawa M, Honda K, Fujii G, Kawashima H, Takekuma K, Hoshika A, Hirohashi S, Yamada T.|
|Title||Beta-catenin interacts with the FUS proto-oncogene product and regulates pre-mRNA splicing.|
BACKGROUND & AIMS:beta-Catenin is a downstream effector of the Wnt signaling pathway and is believed to exert its oncogenic function by activating T-cell factor (TCF)/lymphoid enhancer factor (LEF) family transcriptional factors. However, it is still uncertain whether the diverse effects of beta-catenin are caused solely by aberrant gene transactivation. In this study, we used a proteomics approach to obtain further insight into the functional properties of nuclear beta-catenin.
METHODS:The protein assembly of a native beta-catenin-containing complex in nuclear extracts from a colorectal cancer cell line, DLD-1, was identified using immunoprecipitation and mass spectrometry.
RESULTS:beta-Catenin physically interacted with fusion (FUS)/translocated in liposarcoma (TLS) and various RNA-binding proteins. The expression of FUS/TLS was closely associated with the accumulation of beta-catenin and with the undifferentiated status of intestinal epithelial cells. The transient transfection of FUS suppressed beta-catenin-evoked gene transactivation of TCF/LEF, and beta-catenin transfection affected the splicing pattern of the E1A minigene and induced a novel splicing variant of estrogen receptor (ER)-beta exerting a dominant-negative activity.
CONCLUSIONS:Human cancer expresses a large variety of alternatively spliced messenger RNA (mRNA), but the precise molecular mechanisms responsible for cancer-related alternative splicing are largely unknown. In this study, we demonstrated the interaction of beta-catenin with FUS/TLS and other RNA-binding proteins involved in the regulation of pre-mRNA splicing. Certain mRNA splicing abbreviations seen in human cancers may be induced by the activation of the Wnt signaling pathway.
|MeSH||Alternative Splicing* Cell Line Cell Line, Tumor Colorectal Neoplasms / genetics Cytoskeletal Proteins / metabolism* Humans Kidney Mass Spectrometry Plasmids RNA Precursors / genetics* RNA Splicing / genetics* RNA-Binding Protein FUS / genetics* RNA-Binding Protein FUS / metabolism Trans-Activators / metabolism* beta Catenin / metabolism*|
|Human and Animal Cells||COS-7(RCB0539)|