Stimulation of c‐MYC transcriptional activity and acetylation by recruitment of the cofactor CBP

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Abstract
The c‐MYC oncoprotein regulates various aspects of cell behaviour by modulating gene expression. Here, we report the identification of the cAMP‐response‐element‐binding protein (CBP) as a novel c‐MYC binding partner. The two proteins interact both in vitro and in cells, and CBP binds to the carboxy‐terminal region of c‐MYC. Importantly, CBP, as well as p300, is associated with E‐box‐containing promoter regions of genes that are regulated by c‐MYC. Furthermore, c‐MYC and CBP/p300 function synergistically in the activation of reporter‐gene constructs. Thus, CBP and p300 function as positive cofactors for c‐MYC. In addition, c‐MYC is acetylated in cells. This modification does not require MYC box II, suggesting that it is independent of TRRAP complexes. Instead, CBP acetylates c‐MYC in vitro , and co‐expression of CBP with c‐MYC stimulates in vivo acetylation. Functionally, this results in a decrease in ubiquitination and stabilization of c‐MYC proteins. Thus, CBP and p300 are novel functional binding partners of c‐MYC.