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

dc.contributor.author

Yang, Wei

dc.contributor.author

Sheng, Huaxin

dc.contributor.author

Thompson, J Will

dc.contributor.author

Zhao, Shengli

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Wang, Liangli

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Miao, Pei

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Liu, Xiaozhi

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Moseley, M Arthur

dc.contributor.author

Paschen, Wulf

dc.date.accessioned

2021-06-01T14:07:18Z

dc.date.available

2021-06-01T14:07:18Z

dc.date.issued

2014-04

dc.date.updated

2021-06-01T14:07:17Z

dc.description.abstract

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.
dc.identifier

STROKEAHA.113.004315

dc.identifier.issn

0039-2499

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1524-4628

dc.identifier.uri

https://hdl.handle.net/10161/23276

dc.language

eng

dc.publisher

Ovid Technologies (Wolters Kluwer Health)

dc.relation.ispartof

Stroke

dc.relation.isversionof

10.1161/strokeaha.113.004315

dc.subject

Animals

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Mice, Transgenic

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Mice

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Brain Ischemia

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Ischemic Attack, Transient

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Proteome

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Ubiquitins

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Small Ubiquitin-Related Modifier Proteins

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SUMO-1 Protein

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Proteomics

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RNA Processing, Post-Transcriptional

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Mass Spectrometry

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Stroke

dc.title

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

dc.type

Journal article

duke.contributor.orcid

Yang, Wei|0000-0001-5719-4393

duke.contributor.orcid

Sheng, Huaxin|0000-0002-4325-2940

pubs.begin-page

1115

pubs.end-page

1122

pubs.issue

4

pubs.organisational-group

School of Medicine

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Medicine, Cardiology

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Duke

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Medicine

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Clinical Science Departments

pubs.organisational-group

Faculty

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Anesthesiology

pubs.organisational-group

Pharmacology & Cancer Biology

pubs.organisational-group

Basic Science Departments

pubs.publication-status

Published

pubs.volume

45

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