Acetylation of beta-catenin by CREB-binding protein (CBP).
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.
Wolf
Daniel
D
Wellcome/CRC (Cancer Research Campaign) Institute and Department of Pathology, University of Cambridge, United Kingdom.
Rodova
Marianna
M
Miska
Eric A
EA
Calvet
James P
JP
Kouzarides
Tony
T
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
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