TY - JOUR
T1 - Six lysine residues on c-Myc are direct substrates for acetylation by p300
AU - Zhang, Kangling
AU - Faiola, Francesco
AU - Martinez, Ernest
N1 - Funding Information:
We thank Dr. J. Capone and Dr. E. Lymar for reagents and A. Farina for technical assistance. This work was supported by a NIH grant (CA100464) and by a UCR Genomics Institute Core Instrumentation grant to E.M.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/10/14
Y1 - 2005/10/14
N2 - The c-Myc oncoprotein (Myc) functions as a transcription regulator in association with an obligatory partner, Max, to control cell growth and differentiation. The Myc:Max complex regulates specific genes by recognizing "E-box" DNA sequences and promoter-bound factors such as Miz-1. Myc recruits histone acetyltransferases (HATs) to modify chromatin and is, itself, acetylated in mammalian cells by several of these HATs including p300/CBP, GCN5, and Tip60. The Myc residues that are directly modified by these different HATs remain unknown. Here, we have analyzed the acetylation of recombinant Myc:Max complexes by purified p300 HAT in vitro by using MALDI-TOF and LC-ESI-MS/MS mass spectrometry. These analyses identify six lysine residues in human Myc (K143, K157, K275, K317, K323, and K371) as direct substrates for p300. Our results further indicate that p300 can acetylate DNA-bound Myc:Max complexes and that acetylated Myc:Max heterodimers efficiently interact with Miz-1.
AB - The c-Myc oncoprotein (Myc) functions as a transcription regulator in association with an obligatory partner, Max, to control cell growth and differentiation. The Myc:Max complex regulates specific genes by recognizing "E-box" DNA sequences and promoter-bound factors such as Miz-1. Myc recruits histone acetyltransferases (HATs) to modify chromatin and is, itself, acetylated in mammalian cells by several of these HATs including p300/CBP, GCN5, and Tip60. The Myc residues that are directly modified by these different HATs remain unknown. Here, we have analyzed the acetylation of recombinant Myc:Max complexes by purified p300 HAT in vitro by using MALDI-TOF and LC-ESI-MS/MS mass spectrometry. These analyses identify six lysine residues in human Myc (K143, K157, K275, K317, K323, and K371) as direct substrates for p300. Our results further indicate that p300 can acetylate DNA-bound Myc:Max complexes and that acetylated Myc:Max heterodimers efficiently interact with Miz-1.
KW - Acetylation
KW - Histone acetyltransferase
KW - Mass spectrometry
KW - c-Myc
KW - p300
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U2 - 10.1016/j.bbrc.2005.08.075
DO - 10.1016/j.bbrc.2005.08.075
M3 - Article
C2 - 16126174
AN - SCOPUS:24344451246
SN - 0006-291X
VL - 336
SP - 274
EP - 280
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -