Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Highlight
  • Published:

Gene expression

Reading protein acetylation

Nature Reviews Molecular Cell Biology volume 17, pages 676–677 (2016)Cite this article

Subjects

The tumour suppressor protein p53 is acetylated at multiple Lys residues in the carboxy-terminal domain (CTD). By comparing acetylated and unacetylated p53 CTD peptides, Wang et al. identified the oncoprotein SET as specifically binding to the unacetylated peptide. Expression of CREB-binding protein (CBP), which mediates p53 acetylation, abrogated the binding of SET to wild-type p53 but not to a CTD acetylation-deficient p53 mutant. Thus, p53 CTD acetylation disrupts SET binding, which was further shown to occur through the acidic domain of SET.

SET alone did not bind to DNA, whereas a p53–SET complex did bind to p53 target promoters and repressed the transactivation of a reporter gene compared with p53 alone. Repression of p53-dependent gene expression was abrogated by a SET mutant lacking the acidic domain or by a p53 mutant lacking the CTD. Therefore, SET functions as a transcriptional co-repressor of p53, recognizing its unacetylated form. In line with this, depletion of SET by RNA interference markedly increased the expression of p53 target genes (such as CDKN1A and PUMA) in various human cancer cell lines and induced p53-dependent repression of cell growth. Furthermore, SET depletion of cancer cells expressing wild-type p53, but not p53-deficient cells, suppressed tumour growth in a xenograft model.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Wang, D. et al. Acetylation-regulated interaction between p53 and SET reveals a widespread regulatory mode. Nature http://dx.doi.org/10.1038/nature19759 (2016)

Download references

Authors
  1. Kirsty Minton
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Minton, K. Reading protein acetylation. Nat Rev Mol Cell Biol 17, 676–677 (2016). https://doi.org/10.1038/nrm.2016.137

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrm.2016.137

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing