A Redox-Regulated SUMO/Acetylation Switch of HIPK2 Controls the Survival Threshold to Oxidative Stress

L. de la Vega, I. Grishina, R. Moreno, M. Krüger, T. Braun, M.L. Schmitz (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    72 Citations (Scopus)

    Abstract

    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.
    Original languageEnglish
    Pages (from-to)472-483
    Number of pages12
    JournalMolecular Cell
    Volume46
    Issue number4
    DOIs
    Publication statusPublished - 25 May 2012

    Fingerprint Dive into the research topics of 'A Redox-Regulated SUMO/Acetylation Switch of HIPK2 Controls the Survival Threshold to Oxidative Stress'. Together they form a unique fingerprint.

  • Cite this