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

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‐...

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Bibliographic Details
Published in:EMBO reports 2003-05, Vol.4 (5), p.484-490
Main Authors: Vervoorts, Jörg, Lüscher-Firzlaff, Juliane M, Rottmann, Sabine, Lilischkis, Richard, Walsemann, Gesa, Dohmann, Karen, Austen, Matthias, Lüscher, Bernhard
Format: Article
Language:English
Subjects:
Acetyl Coenzyme A - metabolism
Acetylation
Acetyltransferases - genetics
Acetyltransferases - metabolism
Adaptor Proteins, Signal Transducing
Binding Sites
Cell Cycle Proteins - genetics
Cell Cycle Proteins - metabolism
Cells, Cultured
Cyclic AMP Response Element-Binding Protein - chemistry
Cyclic AMP Response Element-Binding Protein - metabolism
Genes, Reporter
Histone Acetyltransferases
Humans
Nuclear Proteins - metabolism
p300-CBP Transcription Factors
Proteins
Proto-Oncogene Proteins c-myc - chemistry
Proto-Oncogene Proteins c-myc - metabolism
Recombinant Fusion Proteins - metabolism
Scientific Report
Transcription Factors
Transcription, Genetic
Transcriptional Activation
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Summary: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.
ISSN:1469-221X
1469-3178
1469-221X
DOI:10.1038/sj.embor.embor821