Repression of p53 activity by Smyd2-mediated methylation

Jing Huang, Laura Perez-Burgos, Brandon J. Placek, Roopsha Sengupta, Mario Richter, Jean A. Dorsey, Stefan Kubicek, Susanne Opravil, Thomas Jenuwein and Shelley L. Berger ()
Additional contact information
Jing Huang: Gene Expression and Regulation Program, The Wistar Institute
Laura Perez-Burgos: Research Institute of Molecular Pathology (IMP), The Vienna Biocenter
Brandon J. Placek: Gene Expression and Regulation Program, The Wistar Institute
Roopsha Sengupta: Research Institute of Molecular Pathology (IMP), The Vienna Biocenter
Mario Richter: Research Institute of Molecular Pathology (IMP), The Vienna Biocenter
Jean A. Dorsey: Gene Expression and Regulation Program, The Wistar Institute
Stefan Kubicek: Research Institute of Molecular Pathology (IMP), The Vienna Biocenter
Susanne Opravil: Research Institute of Molecular Pathology (IMP), The Vienna Biocenter
Thomas Jenuwein: Research Institute of Molecular Pathology (IMP), The Vienna Biocenter
Shelley L. Berger: Gene Expression and Regulation Program, The Wistar Institute

Nature, 2006, vol. 444, issue 7119, 629-632

Abstract: Abstract Specific sites of lysine methylation on histones correlate with either activation or repression of transcription1,2,3. The tumour suppressor p53 (refs 4–7) is one of only a few non-histone proteins known to be regulated by lysine methylation8. Here we report a lysine methyltransferase, Smyd2, that methylates a previously unidentified site, Lys 370, in p53. This methylation site, in contrast to the known site Lys 372, is repressing to p53-mediated transcriptional regulation. Smyd2 helps to maintain low concentrations of promoter-associated p53. We show that reducing Smyd2 concentrations by short interfering RNA enhances p53-mediated apoptosis. We find that Set9-mediated methylation of Lys 372 inhibits Smyd2-mediated methylation of Lys 370, providing regulatory cross-talk between post-translational modifications. In addition, we show that the inhibitory effect of Lys 372 methylation on Lys 370 methylation is caused, in part, by blocking the interaction between p53 and Smyd2. Thus, similar to histones, p53 is subject to both activating and repressing lysine methylation. Our results also predict that Smyd2 may function as a putative oncogene by methylating p53 and repressing its tumour suppressive function.

Date: 2006
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/nature05287 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:444:y:2006:i:7119:d:10.1038_nature05287

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature05287

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().