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

Jörg Vervoorts; Juliane M Lüscher-Firzlaff; Sabine Rottmann; Richard Lilischkis; Gesa Walsemann; Karen Dohmann; Matthias Austen; Bernhard Lüscher

doi:10.1038/sj.embor.embor821

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

EMBO Rep. 2003 May;4(5):484-90. doi: 10.1038/sj.embor.embor821.

Authors

Jörg Vervoorts¹, Juliane M Lüscher-Firzlaff, Sabine Rottmann, Richard Lilischkis, Gesa Walsemann, Karen Dohmann, Matthias Austen, Bernhard Lüscher

Affiliation

¹ Institut für Molekularbiologie, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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
Proto-Oncogene Proteins c-myc / chemistry
Proto-Oncogene Proteins c-myc / metabolism*
Recombinant Fusion Proteins / metabolism
Transcription Factors
Transcription, Genetic
Transcriptional Activation
p300-CBP Transcription Factors

Substances

Adaptor Proteins, Signal Transducing
Cell Cycle Proteins
Cyclic AMP Response Element-Binding Protein
Nuclear Proteins
Proto-Oncogene Proteins c-myc
Recombinant Fusion Proteins
Transcription Factors
transformation-transcription domain-associated protein
Acetyl Coenzyme A
Acetyltransferases
Histone Acetyltransferases
p300-CBP Transcription Factors
p300-CBP-associated factor