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Molecular and Cellular Biology, December 2004, p. 10826-10834, Vol. 24, No. 24
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.24.10826-10834.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The c-MYC Oncoprotein Is a Substrate of the Acetyltransferases hGCN5/PCAF and TIP60

Jagruti H. Patel,1 Yanping Du,1 Penny G. Ard,1 Charles Phillips,1 Beth Carella,1 Chi-Ju Chen,1 Carrie Rakowski,2 Chandrima Chatterjee,3 Paul M. Lieberman,3 William S. Lane,3 Gerd A. Blobel,2 and Steven B. McMahon1*

The Wistar Institute,1 Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,2 Harvard Microchemistry and Proteomics Analysis Facility, Cambridge, Massachusetts3

Received 18 June 2004/ Returned for modification 19 July 2004/ Accepted 17 September 2004

The c-MYC oncoprotein functions as a sequence-specific transcription factor. The ability of c-MYC to activate transcription relies in part on the recruitment of cofactor complexes containing the histone acetyltransferases mammalian GCN5 (mGCN5)/PCAF and TIP60. In addition to acetylating histones, these enzymes have been shown to acetylate other proteins involved in transcription, including sequence-specific transcription factors. This study was initiated in order to determine whether c-MYC is a direct substrate of mGCN5 and TIP60. We report here that mGCN5/PCAF and TIP60 acetylate c-MYC in vivo. By using nanoelectrospray tandem mass spectrometry to examine c-MYC purified from human cells, the major mGCN5-induced acetylation sites have been mapped. Acetylation of c-MYC by either mGCN5/PCAF or TIP60 results in a dramatic increase in protein stability. The data reported here suggest a conserved mechanism by which acetyltransferases regulate c-MYC function by altering its rate of degradation.

* Corresponding author. Mailing address: The Wistar Institute, 3601 Spruce St., Philadelphia, PA 19104. Phone: (215) 898-3736. Fax: (215) 898-3933. E-mail: smcmahon{at}wistar.upenn.edu.

Molecular and Cellular Biology, December 2004, p. 10826-10834, Vol. 24, No. 24
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.24.10826-10834.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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