2005年10月
beta-catenin interacts with the FUS proto-oncogene product and regulates pre-mRNA splicing
GASTROENTEROLOGY
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- 巻
- 129
- 号
- 4
- 開始ページ
- 1225
- 終了ページ
- 1236
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1053/j.gastro.2005.07.025
- 出版者・発行元
- W B SAUNDERS CO-ELSEVIER INC
Background & Aims: beta-Catenin is a downstream effector of the Writ 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.
- リンク情報
- ID情報
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- DOI : 10.1053/j.gastro.2005.07.025
- ISSN : 0016-5085
- eISSN : 1528-0012
- Web of Science ID : WOS:000232586000012