Cerebral ischemia/stroke and small ubiquitin-like modifier (SUMO) conjugation--a new target for therapeutic intervention?
Journal Article (Journal Article;Review)
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.
Full Text
Duke Authors
Cited Authors
- Yang, W; Sheng, H; Homi, HM; Warner, DS; Paschen, W
Published Date
- August 2008
Published In
Volume / Issue
- 106 / 3
Start / End Page
- 989 - 999
PubMed ID
- 18410505
Pubmed Central ID
- 18410505
Electronic International Standard Serial Number (EISSN)
- 1471-4159
Digital Object Identifier (DOI)
- 10.1111/j.1471-4159.2008.05404.x
Language
- eng
Conference Location
- England