title: Acetylation of beta-catenin by CREB-binding protein (CBP).
abstract: 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.
authors.affiliation: Wellcome/CRC (Cancer Research Campaign) Institute and Department of Pathology, University of Cambridge, United Kingdom.
authors.forename: Daniel
authors.initials: D
authors.lastname: Wolf
authors.forename: Marianna
authors.initials: M
authors.lastname: Rodova
authors.forename: Eric A
authors.initials: EA
authors.lastname: Miska
authors.forename: James P
authors.initials: JP
authors.lastname: Calvet
authors.forename: Tony
authors.initials: T
authors.lastname: Kouzarides
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D001483:Base Sequence; D050882:CREB-Binding Protein; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism*; D017931:DNA Primers; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000378:metabolism*; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D009687:Nuclear Proteins; D015534:Trans-Activators; D051176:beta Catenin; D050882:CREB-Binding Protein; C494363:CREBBP protein, human