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Yeast As a Chassis for Developing Functional Assays to Study Human P53
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Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

Methylation of p53 by Set7/9 mediates p53 acetylation and activity in vivo

Julia K Kurash1, Hong Lei, Qiong Shen

  • 1Epigenetics, Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, MA 02139, USA.

Molecular Cell
|February 19, 2008
PubMed

Insights

The protein methyltransferase Set7/9 is crucial for p53 activation in vivo. Its absence impairs DNA damage response and promotes cancer by preventing p53 methylation and subsequent acetylation.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • The protein methyltransferase Set7/9 (SET Domain Containing 7) has been implicated in regulating p53 activity within cancer cells.
  • The in vivo significance of Set7/9 in modulating p53 function remains largely undetermined.

Purpose of the Study:

  • To investigate the in vivo role of Set7/9 in p53 regulation and its implications for cancer development.
  • To elucidate the mechanistic link between Set7/9-mediated methylation and p53 acetylation.

Main Methods:

  • Generation of a Set7/9 null allele in mice to study its in vivo function.
  • Analysis of p53 methylation and acetylation status in Set7/9 mutant cells.
  • Assessment of p53 downstream target gene induction following DNA damage.
  • Evaluation of oncogenic transformation predisposition in Set7/9 deficient cells.

Main Results:

  • Set7/9 mutant mice cells exhibit a failure to methylate p53 at lysine 369 (K369).
  • These cells demonstrate impaired induction of p53 target genes in response to DNA damage.
  • Set7/9 deficiency leads to a predisposition towards oncogenic transformation.
  • Methylation of p53 by Set7/9 is essential for the recruitment of the acetyltransferase Tip60 and subsequent p53 acetylation.

Conclusions:

  • This study provides the first genetic evidence for the critical role of Set7/9-mediated lysine methylation in p53 activation in vivo.
  • A mechanistic connection between p53 methylation by Set7/9 and its subsequent acetylation by Tip60 has been established.

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