Six lysine residues on c-Myc are direct substrates for acetylation by p300

Kangling Zhang, Francesco Faiola, Ernest Martinez

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)274-280
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume336
Issue number1
DOIs
StatePublished - Oct 14 2005
Externally publishedYes

Fingerprint

Histone Acetyltransferases
Acetylation
Lysine
Substrates
E-Box Elements
Oncogene Proteins
DNA sequences
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Cell growth
Transcription
Chromatin
Mass spectrometry
Cell Differentiation
Mass Spectrometry
Genes
Cells
Association reactions
DNA
Growth

Keywords

  • Acetylation
  • c-Myc
  • Histone acetyltransferase
  • Mass spectrometry
  • p300

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Six lysine residues on c-Myc are direct substrates for acetylation by p300. / Zhang, Kangling; Faiola, Francesco; Martinez, Ernest.

In: Biochemical and Biophysical Research Communications, Vol. 336, No. 1, 14.10.2005, p. 274-280.

Research output: Contribution to journalArticle

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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.

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