Cerebral ischemia/stroke and small ubiquitin-like modifier (SUMO) conjugation--a new target for therapeutic intervention?

J Neurochem. 2008 Aug;106(3):989-99. doi: 10.1111/j.1471-4159.2008.05404.x. Epub 2008 Apr 10.


Transient cerebral ischemia/stroke activates various post-translational protein modifications such as phosphorylation and ubiquitin conjugation that are believed to play a major role in the pathological process triggered by an interruption of blood supply and culminating in cell death. A new system of post-translational protein modification has been identified, termed as small ubiquitin-like modifier (SUMO) conjugation. Like ubiquitin, SUMO is conjugated to the lysine residue of target proteins in a complex process. This review summarizes observations from recent experiments focusing on the effect of cerebral ischemia on SUMO conjugation. Transient global and focal cerebral ischemia both induced a rapid, dramatic and long-lasting rise in levels of SUMO2/3 conjugation. After transient focal cerebral ischemia, SUMO conjugation was particularly prominent in neurons located at the border of the ischemic territory where SUMO-conjugated proteins translocated to the nucleus. Many SUMO conjugation target proteins are transcription factors and sumoylation has been shown to have a major impact on the activity, stability, and cellular localization of target proteins. The rise in levels of SUMO-conjugated proteins is therefore likely to have a major effect on the fate of post-ischemic neurons. The sumoylation process could provide an exciting new target for therapeutic intervention.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain Ischemia / drug therapy
  • Brain Ischemia / metabolism*
  • Drug Delivery Systems / methods
  • Drug Delivery Systems / trends*
  • Humans
  • Pharmaceutical Preparations / administration & dosage
  • SUMO-1 Protein / antagonists & inhibitors
  • SUMO-1 Protein / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Stroke / drug therapy
  • Stroke / metabolism*


  • Pharmaceutical Preparations
  • SUMO-1 Protein