Stimulation of c‐MYC transcriptional activity and acetylation by recruitment of the cofactor CBP
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- Jörg Vervoorts
- Institut für Molekularbiologie, Medizinische Hochschule Hannover Carl‐Neuberg‐Strasse 1 30625 Hannover Germany
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- Juliane M Lüscher‐Firzlaff
- Abteilung Biochemie und Molekularbiologie, Institut für Biochemie, Klinikum der RWTH Pauwelsstrasse 30 52057 Aachen Germany
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- Sabine Rottmann
- Abteilung Biochemie und Molekularbiologie, Institut für Biochemie, Klinikum der RWTH Pauwelsstrasse 30 52057 Aachen Germany
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- Richard Lilischkis
- Abteilung Biochemie und Molekularbiologie, Institut für Biochemie, Klinikum der RWTH Pauwelsstrasse 30 52057 Aachen Germany
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- Gesa Walsemann
- Abteilung Biochemie und Molekularbiologie, Institut für Biochemie, Klinikum der RWTH Pauwelsstrasse 30 52057 Aachen Germany
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- Karen Dohmann
- Institut für Molekularbiologie, Medizinische Hochschule Hannover Carl‐Neuberg‐Strasse 1 30625 Hannover Germany
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- Matthias Austen
- Institut für Molekularbiologie, Medizinische Hochschule Hannover Carl‐Neuberg‐Strasse 1 30625 Hannover Germany
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- Bernhard Lüscher
- Abteilung Biochemie und Molekularbiologie, Institut für Biochemie, Klinikum der RWTH Pauwelsstrasse 30 52057 Aachen Germany
抄録
<jats:p>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 <jats:italic>in vitro</jats:italic> 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 <jats:italic>in vitro</jats:italic>, and co‐expression of CBP with c‐MYC stimulates <jats:italic>in vivo</jats:italic> 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.</jats:p>
収録刊行物
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- EMBO reports
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EMBO reports 4 (5), 484-490, 2003-04-04
Springer Science and Business Media LLC
