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J. Biol. Chem. 275 (45): 35170-35175

© 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

Regulation of Lef-mediated Transcription and p53-dependent Pathway by Associating beta -Catenin with CBP/p300*

Makoto MiyagishiDagger §, Ryouji FujiiDagger §, Mitsutoki HattaDagger §, Eisaku Yoshida§, Natsumi ArayaDagger §, Akira Nagafuchi, Satoru Ishihara, Toshihiro NakajimaDagger §, and Akiyoshi FukamizuDagger §||

From the Dagger  Center for Tsukuba Advanced Research Alliance, § Institute of Applied Biochemistry, University of Tsukuba, Tsukuba, Ibaraki 305-8577, and the  Department of Cell Biology, Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan

CBP and its homologue p300 play significant roles in cell differentiation, cell cycle, and anti-oncogenesis. We demonstrated that beta -catenin, recently known as a potent oncogene, and CBP/p300 are associated through its CH3 region, which is a primary target of adenoviral oncoprotein E1A and various nuclear proteins, such as p53, cyclin E, and AP-1, and both are colocalized in the nuclear bodies. CBP/p300 potentiated Lef-mediated transactivation of beta -catenin, and E1A, a potent inhibitor of CBP/p300, repressed its transactivation. Furthermore, overexpression of stable beta -catenin mutant competitively suppressed the p53-dependent pathway. These may be a key mechanism of beta -catenin involved in oncogenic events underlying disruption of tumor suppressor function through CBP/p300.

* This work was supported by grants from the "Research for the Future" Program (The Japan Society for the Promotion of Science: JSPS-RFTF 97L00804); the Ministry of Education, Science, Sports, and Culture of Japan; The Asahi Glass Foundation; and The Nissan Science Foundation.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

|| To whom correspondence should be addressed: Center for Tsukuba Advanced Research Alliance, Institute of Applied Biochemistry, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan. Tel.:/Fax: 81-298-53-6070; E-mail: akif@tara.tsukuba.ac.jp.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

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