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Originally published In Press as doi:10.1074/jbc.M201196200 on April 24, 2002

J. Biol. Chem., Vol. 277, Issue 28, 25562-25567, July 12, 2002
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Acetylation of beta -Catenin by CREB-binding Protein (CBP)*

Daniel WolfDagger §, Marianna Rodova§||, Eric A. MiskaDagger , James P. Calvet||**, and Tony KouzaridesDagger Dagger Dagger

From the Dagger  Wellcome/CRC (Cancer Research Campaign) Institute and Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, United Kingdom and || The University of Kansas Medical Center, Kansas City, Kansas 66160

Acetylation controls the activity of numerous proteins involved in regulating gene transcription as well as many other cellular processes. In this report we show that the CREB-binding protein (CBP) acetyltransferase acetylates beta -catenin protein in vivo. beta -Catenin is a central component of the Wnt signaling pathway, which is of key importance in development as well as being heavily implicated in a variety of human cancers. We show that the CBP-mediated acetylation of beta -catenin occurs at a single site, lysine 49. Importantly, this lysine is frequently found mutated in cancer and is in a region of importance to the regulation of beta -catenin. We show that mutation of this site leads specifically to an increase in the ability of beta -catenin to activate the c-myc gene but not other beta -catenin-regulated genes. This suggests that acetylation of beta -catenin is involved in regulating Wnt signaling in a promoter-specific fashion.

* This work was supported in part by a grant from the Cancer Research Campaign.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.

§ Both authors contributed equally to this work.

Supported by the Peter Wildy studentship of Gonville and Cauis College Cambridge.

** Supported by National Institutes of Health Grants DK53763 and DK57301 and a Lied Endowed Basic Science Pilot Research Grant.

Dagger Dagger To whom correspondence should be addressed. Tel.: 44-1223-334111; Fax: 44-1223-334089; E-mail: tk106@mole.bio.cam.ac.uk.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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