Crosstalk between sumoylation and acetylation regulates p53-dependent chromatin transcription and DNA binding

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Covalent modification by small ubiquitin-related modifiers (SUMO) regulates p53 transcription activity through an undefined mechanism. Using reconstituted sumoylation components, we purified SUMO-1-conjugated p53 (Su-p53) to near homogeneity. Su-p53 exists in solution as a tetramer and interacts with p300 histone acetyltransferase as efficiently as the unmodified protein. Nevertheless, it fails to activate p53-dependent chromatin transcription because of its inability to bind DNA. With sequential modification assays, we found that sumoylation of p53 at K386 blocks subsequent acetylation by p300, whereas p300-acetylated p53 remains permissive for ensuing sumoylation at K386 and alleviates sumoylation-inhibited DNA binding. While preventing the free form of p53 from accessing its cognate sites, sumoylation fails to disengage prebound p53 from DNA. The sumoylation-deficient K386R protein, when expressed in p53-null cells, exhibits higher transcription activity and binds better to the endogenous p21 gene compared with the wild-type protein. These studies unravel a molecular mechanism underlying sumoylation-regulated p53 function and further uncover a new role of acetylation in antagonizing the inhibitory effect of sumoylation on p53 binding to DNA.

Original languageEnglish (US)
Pages (from-to)1246-1259
Number of pages14
JournalEMBO Journal
Volume28
Issue number9
DOIs
StatePublished - May 6 2009

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Sumoylation
Acetylation
Transcription
Crosstalk
Chromatin
DNA
Ubiquitin
Histone Acetyltransferases
Proteins
Assays
Genes
Null Lymphocytes

Keywords

  • Acetylation
  • Chromatin transcription
  • P53
  • SUMO-1
  • Sumoylation

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Medicine(all)

Cite this

Crosstalk between sumoylation and acetylation regulates p53-dependent chromatin transcription and DNA binding. / Wu, Shwu Yuan; Chiang, Cheng Ming.

In: EMBO Journal, Vol. 28, No. 9, 06.05.2009, p. 1246-1259.

Research output: Contribution to journalArticle

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