Dual regulation of c-Myc by p300 via acetylation-dependent control of Myc protein turnover and coactivation of Myc-induced transcription

Francesco Faiola, Xiaohui Liu, Szuying Lo, Songqin Pan, Kangling Zhang, Elena Lymar, Anthony Farina, Ernest Martinez

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

The c-Myc oncoprotein (Myc) controls cell fate by regulating gene transcription in association with a DNA-binding partner, Max. While Max lacks a transcription regulatory domain, the N terminus of Myc contains a transcription activation domain (TAD) that recruits cofactor complexes containing the histone acetyltransferases (HATs) GCN5 and Tip60. Here, we report a novel functional interaction between Myc TAD and the p300 coactivator-acetyltransferase. We show that p300 associates with Myc in mammalian cells and in vitro through direct interactions with Myc TAD residues 1 to 110 and acetylates Myc in a TAD-dependent manner in vivo at several lysine residues located between the TAD and DNA-binding domain. Moreover, the Myc:Max complex is differentially acetylated by p300 and GCN5 and is not acetylated by Tip60 in vitro, suggesting distinct functions for these acetyltransferases. Whereas p300 and CBP can stabilize Myc independently of acetylation, p300-mediated acetylation results in increased Myc turnover. In addition, p300 functions as a coactivator that is recruited by Myc to the promoter of the human telomerase reverse transcriptase gene, and p300/CBP stimulates Myc TAD-dependent transcription in a HAT domain-dependent manner. Our results suggest dual roles for p300/CBP in Myc regulation: as a Myc coactivator that stabilizes Myc and as an inducer of Myc instability via direct Myc acetylation.

Original languageEnglish (US)
Pages (from-to)10220-10234
Number of pages15
JournalMolecular and Cellular Biology
Volume25
Issue number23
DOIs
StatePublished - Dec 2005
Externally publishedYes

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Acetylation
Transcriptional Activation
Proteins
Histone Acetyltransferases
Acetyltransferases
Oncogene Proteins
DNA
Genes
Lysine

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Dual regulation of c-Myc by p300 via acetylation-dependent control of Myc protein turnover and coactivation of Myc-induced transcription. / Faiola, Francesco; Liu, Xiaohui; Lo, Szuying; Pan, Songqin; Zhang, Kangling; Lymar, Elena; Farina, Anthony; Martinez, Ernest.

In: Molecular and Cellular Biology, Vol. 25, No. 23, 12.2005, p. 10220-10234.

Research output: Contribution to journalArticle

Faiola, Francesco ; Liu, Xiaohui ; Lo, Szuying ; Pan, Songqin ; Zhang, Kangling ; Lymar, Elena ; Farina, Anthony ; Martinez, Ernest. / Dual regulation of c-Myc by p300 via acetylation-dependent control of Myc protein turnover and coactivation of Myc-induced transcription. In: Molecular and Cellular Biology. 2005 ; Vol. 25, No. 23. pp. 10220-10234.
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AU - Lymar, Elena

AU - Farina, Anthony

AU - Martinez, Ernest

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