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Small ubiquitin-like modifier 3-modified proteome regulated by brain ischemia in novel small ubiquitin-like modifier transgenic mice: putative protective proteins/pathways.

Publication ,  Journal Article
Yang, W; Sheng, H; Thompson, JW; Zhao, S; Wang, L; Miao, P; Liu, X; Moseley, MA; Paschen, W
Published in: Stroke
April 2014

BACKGROUND AND PURPOSE: Small ubiquitin-like modifier (SUMO) conjugation is a post-translational modification associated with many human diseases. Characterization of the SUMO-modified proteome is pivotal to define the mechanistic link between SUMO conjugation and such diseases. This is particularly evident for SUMO2/3 conjugation, which is massively activated after brain ischemia/stroke, and is believed to be a protective response. The purpose of this study was to perform a comprehensive analysis of the SUMO3-modified proteome regulated by brain ischemia using a novel SUMO transgenic mouse. METHODS: To enable SUMO proteomics analysis in vivo, we generated transgenic mice conditionally expressing tagged SUMO1-3 paralogues. Transgenic mice were subjected to 10 minutes forebrain ischemia and 1 hour of reperfusion. SUMO3-conjugated proteins were enriched by anti-FLAG affinity purification and analyzed by liquid chromatography-tandem mass spectrometry. RESULTS: Characterization of SUMO transgenic mice demonstrated that all 3 tagged SUMO paralogues were functionally active, and expression of exogenous SUMOs did not modify the endogenous SUMOylation machinery. Proteomics analysis identified 112 putative SUMO3 substrates of which 91 candidates were more abundant in the ischemia group than the sham group. Data analysis revealed processes/pathways with putative neuroprotective functions, including glucocorticoid receptor signaling, RNA processing, and SUMOylation-dependent ubiquitin conjugation. CONCLUSIONS: The identified proteins/pathways modulated by SUMOylation could be the key to understand the mechanisms linking SUMOylation to neuroprotection, and thus provide new promising targets for therapeutic interventions. The new transgenic mouse will be an invaluable platform for analyzing the SUMO-modified proteome in models of human disorders and thereby help to mechanistically link SUMOylation to the pathological processes.

Duke Scholars

Published In

Stroke

DOI

EISSN

1524-4628

Publication Date

April 2014

Volume

45

Issue

4

Start / End Page

1115 / 1122

Location

United States

Related Subject Headings

  • Ubiquitins
  • Stroke
  • Small Ubiquitin-Related Modifier Proteins
  • SUMO-1 Protein
  • RNA Processing, Post-Transcriptional
  • Proteomics
  • Proteome
  • Neurology & Neurosurgery
  • Mice, Transgenic
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Yang, W., Sheng, H., Thompson, J. W., Zhao, S., Wang, L., Miao, P., … Paschen, W. (2014). Small ubiquitin-like modifier 3-modified proteome regulated by brain ischemia in novel small ubiquitin-like modifier transgenic mice: putative protective proteins/pathways. Stroke, 45(4), 1115–1122. https://doi.org/10.1161/STROKEAHA.113.004315
Yang, Wei, Huaxin Sheng, J Will Thompson, Shengli Zhao, Liangli Wang, Pei Miao, Xiaozhi Liu, M Arthur Moseley, and Wulf Paschen. “Small ubiquitin-like modifier 3-modified proteome regulated by brain ischemia in novel small ubiquitin-like modifier transgenic mice: putative protective proteins/pathways.Stroke 45, no. 4 (April 2014): 1115–22. https://doi.org/10.1161/STROKEAHA.113.004315.
Yang, Wei, et al. “Small ubiquitin-like modifier 3-modified proteome regulated by brain ischemia in novel small ubiquitin-like modifier transgenic mice: putative protective proteins/pathways.Stroke, vol. 45, no. 4, Apr. 2014, pp. 1115–22. Pubmed, doi:10.1161/STROKEAHA.113.004315.
Yang W, Sheng H, Thompson JW, Zhao S, Wang L, Miao P, Liu X, Moseley MA, Paschen W. Small ubiquitin-like modifier 3-modified proteome regulated by brain ischemia in novel small ubiquitin-like modifier transgenic mice: putative protective proteins/pathways. Stroke. 2014 Apr;45(4):1115–1122.

Published In

Stroke

DOI

EISSN

1524-4628

Publication Date

April 2014

Volume

45

Issue

4

Start / End Page

1115 / 1122

Location

United States

Related Subject Headings

  • Ubiquitins
  • Stroke
  • Small Ubiquitin-Related Modifier Proteins
  • SUMO-1 Protein
  • RNA Processing, Post-Transcriptional
  • Proteomics
  • Proteome
  • Neurology & Neurosurgery
  • Mice, Transgenic
  • Mice