title: Cerebral ischemia/stroke and small ubiquitin-like modifier (SUMO) conjugation--a new target for therapeutic intervention?
abstract: 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.
authors.affiliation: Multidisciplinary Neuroprotection Laboratories, Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Huaxin
authors.initials: H
authors.lastname: Sheng
authors.forename: H Mayumi
authors.initials: HM
authors.lastname: Homi
authors.forename: David S
authors.initials: DS
authors.lastname: Warner
authors.forename: Wulf
authors.initials: W
authors.lastname: Paschen
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods / Q000639:trends*; D006801:Humans; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D025842:SUMO-1 Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D020521:Stroke / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D004364:Pharmaceutical Preparations; D025842:SUMO-1 Protein