Max is acetylated by p300 at several nuclear localization residues

Francesco Faiola, Yi Ting Wu, Songqin Pan, Kangling Zhang, Anthony Farina, Ernest Martinez

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Max is a ubiquitous transcription factor with a bHLHZip [basic HLH (helix-loop-helix) leucine zipper] DNA-binding/dimerization domain and the central component of the Myc/Max/Mad transcription factor network that controls cell growth, proliferation, differentiation and apoptotic cell death in metazoans. Max is the obligatory DNA-binding and dimerization partner for all the bHLHZip regulators of the Myc/Max/Mad network, including the Myc family of oncoproteins and the Mad family of Myc antagonists, which recognize E-box DNA elements in the regulatory regions of target genes. Max lacks a transcription regulatory domain and is the only member of the network that efficiently homodimerizes. Binding of Max homodimers to E-box elements suppresses the transcription regulatory functions of its network partners and of other non-network E-box-binding regulators. In contrast with its highly regulated partners, Max is a constitutively expressed and phosphorylated protein. Phosphorylation is, however, the only Max post-translational modification identified so far. In the present study, we have analysed Max post-translational modifications by MS. We have found that Max is acetylated at several lysine residues (Lys-57, Lys-144 and Lys-145) in mammalian cells. Max acetylation is stimulated by inhibitors of histone deacetylases and by overexpression of the p300 co-activator/HAT (histone acetyltransferase). The p300 HAT also directly acetylates Max in vitro at these three residues. Interestingly, the three Max residues acetylated in vivo and in vitro by p300 are important for Max nuclear localization and Max-mediated suppression of Myc transactivation. These results uncover novel post-translational modifications of Max and suggest the potential regulation of specific Max complexes by p300 and reversible acetylation.

Original languageEnglish (US)
Pages (from-to)397-407
Number of pages11
JournalBiochemical Journal
Volume403
Issue number3
DOIs
StatePublished - May 1 2007
Externally publishedYes

Fingerprint

Post Translational Protein Processing
E-Box Elements
Acetylation
Dimerization
Transcription
DNA
Transcription Factors
Histone Acetyltransferases
Leucine Zippers
Phosphorylation
Histone Deacetylases
Nucleic Acid Regulatory Sequences
Oncogene Proteins
Cell growth
Cell death
Transcriptional Activation
Lysine
Cell Death
Genes
Cells

Keywords

  • Histone acetyltransferase
  • Max
  • MS
  • Myc
  • Nuclear localization
  • p300

ASJC Scopus subject areas

  • Biochemistry
  • Medicine(all)

Cite this

Faiola, F., Wu, Y. T., Pan, S., Zhang, K., Farina, A., & Martinez, E. (2007). Max is acetylated by p300 at several nuclear localization residues. Biochemical Journal, 403(3), 397-407. https://doi.org/10.1042/BJ20061593

Max is acetylated by p300 at several nuclear localization residues. / Faiola, Francesco; Wu, Yi Ting; Pan, Songqin; Zhang, Kangling; Farina, Anthony; Martinez, Ernest.

In: Biochemical Journal, Vol. 403, No. 3, 01.05.2007, p. 397-407.

Research output: Contribution to journalArticle

Faiola, F, Wu, YT, Pan, S, Zhang, K, Farina, A & Martinez, E 2007, 'Max is acetylated by p300 at several nuclear localization residues', Biochemical Journal, vol. 403, no. 3, pp. 397-407. https://doi.org/10.1042/BJ20061593
Faiola, Francesco ; Wu, Yi Ting ; Pan, Songqin ; Zhang, Kangling ; Farina, Anthony ; Martinez, Ernest. / Max is acetylated by p300 at several nuclear localization residues. In: Biochemical Journal. 2007 ; Vol. 403, No. 3. pp. 397-407.
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