The c-MYC oncoprotein is a substrate of the acetyltransferases hGCN5/PCAF and TIP60.
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.
Patel
Jagruti H
JH
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Du
Yanping
Y
Ard
Penny G
PG
Phillips
Charles
C
Carella
Beth
B
Chen
Chi-Ju
CJ
Rakowski
Carrie
C
Chatterjee
Chandrima
C
Lieberman
Paul M
PM
Lane
William S
WS
Blobel
Gerd A
GA
McMahon
Steven B
SB
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
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