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A redox-regulated SUMO/acetylation switch of HIPK2 controls the survival threshold to oxidative stress

Laureano de la Vega1, Inna Grishina, Rita Moreno

  • 1Institute of Biochemistry, Medical Faculty, Justus-Liebig-University, Giessen, Germany.

Molecular Cell
|April 17, 2012
PubMed

Insights

Reactive oxygen species (ROS) signal or kill cells. This study reveals how ROS-induced acetylation of HIPK2 kinase determines cell death sensitivity by regulating oxidative stress levels.

Area of Science:

  • Cellular biology
  • Biochemistry
  • Molecular mechanisms of cell death

Background:

  • Reactive oxygen species (ROS) play dual roles in cell signaling and death.
  • Understanding the molecular thresholds for ROS-mediated cell death is crucial.

Purpose of the Study:

  • To identify the molecular mechanism controlling the threshold between ROS sensitivity and resistance.
  • To investigate the role of HIPK2 acetylation in regulating oxidative stress response.

Main Methods:

  • Investigated ROS-induced post-translational modifications of HIPK2.
  • Utilized SUMOylation and acetylation assays.
  • Employed reconstitution experiments with HIPK2 mutants.

Main Results:

  • HIPK2 acetylation, triggered by elevated ROS, determines cell death sensitivity.
  • SUMOylation of HIPK2 at lower ROS levels maintains a nonacetylated state via HDAC3.
  • Acetylation of HIPK2 leads to decreased ROS levels and promotes cell survival.
  • A non-acetylatable HIPK2 mutant increased ROS-induced cell death, while an acetylation-mimicking mutant promoted survival.

Conclusions:

  • ROS-induced acetylation of HIPK2 is a key mechanism controlling the cell's response to oxidative stress.
  • HIPK2 acetylation acts as a survival switch, preventing cell death under high oxidative stress.

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