The c-MYC oncoprotein is a substrate of the acetyltransferases hGCN5/PCAF and TIP60

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

284 Scopus citations

Abstract

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 mGCNS/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.

Original languageEnglish
Pages (from-to)10826-10834
Number of pages9
JournalMolecular and Cellular Biology
Volume24
Issue number24
DOIs
StatePublished - Dec 2004

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