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

Published

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