Beta-catenin interacts with the FUS proto-oncogene product and regulates pre-mRNA splicing.
OBJECTIVE
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.
Sato
Satoshi
S
Chemotherapy Division and Cancer Proteomics Project, National Cancer Center Research Institute, Tokyo, Japan.
Idogawa
Masashi
M
Honda
Kazufumi
K
Fujii
Gen
G
Kawashima
Hisashi
H
Takekuma
Kouji
K
Hoshika
Akinori
A
Hirohashi
Setsuo
S
Yamada
Tesshi
T
D017398:Alternative Splicing; D002460:Cell Line; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D006801:Humans; D007668:Kidney; D013058:Mass Spectrometry; D010957:Plasmids; D000090063:Proto-Oncogene Mas; D012322:RNA Precursors / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*; D034702:RNA-Binding Protein FUS / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012322:RNA Precursors; D034702:RNA-Binding Protein FUS; D015534:Trans-Activators; D051176:beta Catenin