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Lysine methylation regulates E2F1-induced cell death

Haroula Kontaki1, Iannis Talianidis

  • 1Biomedical Sciences Research Center Al. Fleming, 16672 Vari, Greece.

Molecular Cell
|July 7, 2010
PubMed

Insights

Histone-modifying enzymes Set9 and LSD1 control cell death pathways. Set9 methylation of E2F1 prevents apoptosis, while LSD1 removal of this mark promotes it, revealing opposing roles in tumor cells.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Cancer Research

Background:

  • Histone-modifying enzymes regulate DNA damage responses and apoptosis via p53.
  • The roles of Set9 and LSD1 in p53-deficient cells remain unclear.

Purpose of the Study:

  • To investigate the opposing roles of Set9 and LSD1 in DNA damage-induced cell death in p53-deficient tumor cells.
  • To elucidate the mechanism by which Set9 and LSD1 modulate E2F1 stabilization and apoptosis.

Main Methods:

  • Western blotting to assess protein levels and modifications.
  • Immunoprecipitation to study protein interactions.
  • Cell viability assays to measure apoptosis.

Main Results:

  • Set9 methylates E2F1 at lysine-185, inhibiting its accumulation and pro-apoptotic function during DNA damage.
  • LSD1 removes the Set9 methyl mark, promoting E2F1 stabilization and apoptosis.
  • Methylation at lysine-185 inhibits other modifications (acetylation, phosphorylation) and promotes ubiquitination, leading to E2F1 degradation.

Conclusions:

  • Set9 and LSD1 exhibit opposing functions in regulating DNA damage-induced apoptosis in p53-deficient cells through E2F1 modulation.
  • Crosstalk between methylation and other post-translational modifications dictates E2F1 stability and apoptotic outcome.
  • Methyltransferase function can have context-dependent, opposing biological effects based on target specificity.

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