title: The c-MYC oncoprotein is a substrate of the acetyltransferases hGCN5/PCAF and TIP60.
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 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.
authors.affiliation: The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Jagruti H
authors.initials: JH
authors.lastname: Patel
authors.forename: Yanping
authors.initials: Y
authors.lastname: Du
authors.forename: Penny G
authors.initials: PG
authors.lastname: Ard
authors.forename: Charles
authors.initials: C
authors.lastname: Phillips
authors.forename: Beth
authors.initials: B
authors.lastname: Carella
authors.forename: Chi-Ju
authors.initials: CJ
authors.lastname: Chen
authors.forename: Carrie
authors.initials: C
authors.lastname: Rakowski
authors.forename: Chandrima
authors.initials: C
authors.lastname: Chatterjee
authors.forename: Paul M
authors.initials: PM
authors.lastname: Lieberman
authors.forename: William S
authors.initials: WS
authors.lastname: Lane
authors.forename: Gerd A
authors.initials: GA
authors.lastname: Blobel
authors.forename: Steven B
authors.initials: SB
authors.lastname: McMahon
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D000595:Amino Acid Sequence; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D006207:Half-Life; D051548:Histone Acetyltransferases; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology; D000074443:Lysine Acetyltransferase 5; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D016271:Proto-Oncogene Proteins c-myc / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D013379:Substrate Specificity; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
chemical_list: D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D051548:Histone Acetyltransferases; D000074443:Lysine Acetyltransferase 5; D016271:Proto-Oncogene Proteins c-myc; D015534:Trans-Activators; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C501179:KAT2A protein, human; C098489:KAT5 protein, human