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

Mol Cell. 2012 May 25;46(4):472-83. doi: 10.1016/j.molcel.2012.03.003. Epub 2012 Apr 12.


Moderate concentrations of reactive oxygen species (ROS) serve as coregulatory signaling molecules, whereas exceedingly high concentrations trigger cell death. Here, we identify ROS-induced acetylation of the proapoptotic kinase HIPK2 as a molecular mechanism that controls the threshold discerning sensitivity from resistance toward ROS-mediated cell death. SUMOylation of HIPK2 at permissive ROS concentrations allows the constitutive association of HDAC3 and keeps HIPK2 in the nonacetylated state. Elevated ROS concentrations prevent SUMOylation of HIPK2 and, consequently, reduce association of HDAC3, thus leading to the acetylation of HIPK2. Reconstitution experiments showed that HIPK2-dependent genes cause decreased ROS levels. Although a nonacetylatable HIPK2 mutant enhanced ROS-induced cell death, an acetylation-mimicking variant ensured cell survival even under conditions of high oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Nucleus / metabolism
  • Cell Survival / physiology
  • HEK293 Cells
  • Histone Deacetylases / metabolism
  • Humans
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism
  • Oxidation-Reduction
  • Oxidative Stress
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Sumoylation


  • Carrier Proteins
  • Mutant Proteins
  • Reactive Oxygen Species
  • HIPK2 protein, human
  • Protein Serine-Threonine Kinases
  • Histone Deacetylases
  • histone deacetylase 3