EBP50, a β-catenin-associating protein, enhances Wnt signaling and is over-expressed in hepatocellular carcinoma

作者: Tatsuhiro Shibata , Makoto Chuma , Akiko Kokubu , Michiie Sakamoto , Setsuo Hirohashi

DOI: 10.1053/JHEP.2003.50270

关键词:

摘要: Wnt signaling mediated by β-catenin plays crucial roles in the development of hepatocellular carcinoma and other cancers such as colorectal cancer. β-Catenin associates with T-cell factor (TCF) transcription factors functions a transcriptional activator nucleus. By protein interaction screening, we identified EBP50, cytoplasmic 2 PDZ domains, β-catenin-associating molecule. EBP50 interacted through its carboxyl-PDZ domain vitro vivo. Northern blot RT-PCR analysis revealed an increase messenger RNA (mRNA) (HCC) cell lines surgical specimens human HCC. Over-expression focal nuclear localization was detected In HCC cancer lines, enhanced β-catenin/TCF-dependent dose-dependent manner. line, over-expression carboxyl resulted decrease endogenous β-catenin/TCF transactivation. promoted β-catenin-mediated transactivation only cells which already stabilized, suggesting that may work stabilized for regulation. conclusion, EBP50/β-catenin complex promotes signaling, cooperatively liver

参考文章(43)
B Gumbiner, Signal transduction of beta-catenin. Current Opinion in Cell Biology. ,vol. 7, pp. 634- 640 ,(1995) , 10.1016/0955-0674(95)80104-9
Tracy T. Cao, Heather W. Deacon, David Reczek, Anthony Bretscher, Mark von Zastrow, A kinase-regulated PDZ-domain interaction controls endocytic sorting of the β2-adrenergic receptor Nature. ,vol. 401, pp. 286- 290 ,(1999) , 10.1038/45816
Osamu Tetsu, Frank McCormick, Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature. ,vol. 398, pp. 422- 426 ,(1999) , 10.1038/18884
Yasuo Miyoshi, Yutaka Nagasawa, Yo Sasaki, Takashi Shimano, Tomohiko Aihara, Shingi Imaoka, Yusuke Nakamura, Kyoko Iwao, Masaru Murata, Activation of the β-Catenin Gene in Primary Hepatocellular Carcinomas by Somatic Alterations Involving Exon 3 Cancer Research. ,vol. 58, pp. 2524- 2527 ,(1998)
Masanobu Oshima, Masanobu Oshima, Yoshitaka Tamai, Naomoto Harada, Naomi Murai, Makoto Mark Taketo, Hiroyuki Miyoshi, Hiroko Oshima, Hiroko Oshima, Lack of Tumorigenesis in the Mouse Liver after Adenovirus-mediated Expression of a Dominant Stable Mutant of β-Catenin Cancer Research. ,vol. 62, pp. 1971- 1977 ,(2002)
Hirohisa Yano, Masafumi Maruiwa, Tatsuo Murakami, Kazunori Fukuda, Yuji Ito, Shigetaka Sugihara, Masamichi Kojiro, A NEW HUMAN PLEOMORPHIC HEPATOCELLULAR CARCINOMA CELL LINE, KYN-2 Pathology International. ,vol. 38, pp. 953- 966 ,(1988) , 10.1111/J.1440-1827.1988.TB02368.X
K. M. Cadigan, R. Nusse, Wnt signaling: a common theme in animal development Genes & Development. ,vol. 11, pp. 3286- 3305 ,(1997) , 10.1101/GAD.11.24.3286
Z Songyang, AS Fanning, C Fu, J Xu, SM Marfatia, AH Chishti, A Crompton, AC Chan, JM Anderson, LC Cantley, Recognition of unique carboxyl-terminal motifs by distinct PDZ domains Science. ,vol. 275, pp. 73- 77 ,(1997) , 10.1126/SCIENCE.275.5296.73
A. d. L. Coste, B. Romagnolo, P. Billuart, C.-A. Renard, M.-A. Buendia, O. Soubrane, M. Fabre, J. Chelly, C. Beldjord, A. Kahn, C. Perret, SOMATIC MUTATIONS OF THE BETA -CATENIN GENE ARE FREQUENT IN MOUSE AND HUMAN HEPATOCELLULAR CARCINOMAS Proceedings of the National Academy of Sciences of the United States of America. ,vol. 95, pp. 8847- 8851 ,(1998) , 10.1073/PNAS.95.15.8847