Sumoylation, the covalent attachment of small ubiquitin-like modifier (SUMO) to cellular proteins, has emerged as an important signaling mechanism for regulating protein activity, stability/degradation, subcellular localization, and protein-protein interaction. Like ubiquitination, sumoylation is a dynamic and reversible post-translational modification that is controlled by opposing actions of sumoylating enzymes and SUMO proteases (also known as desumoylating enzymes). Sumoylation plays a critical role in regulation of numerous cellular processes, from transcriptional regulation and DNA repair to protein trafficking, mitochondrial dynamics, and apoptosis. Dysregulated sumoylation has been implicated in a variety of human diseases, including cancer, diabetes, heart disease, and neurodegenerative disorders such as Alzheimer and Parkinson diseases. Despite increasing evidence supporting the importance of sumoylation to human health and disease, our knowledge about the sumoylation/desumoylation machinery components and their cellular functions is limited. In this project, the applicant's team will use a combination of biochemical, proteomic, cell biological, and mouse genetic approaches to study a novel SUMO protease and its signaling role in cellular defense against oxidative stress and apoptosis. The results of the proposed studies should advance our knowledge of the fundamental mechanisms governing SUMO signaling in all eukaryotic cells and provide a molecular basis for understanding and treating a diverse array of human diseases that involve dysregulated sumoylation.

Public Health Relevance

The importance of proper sumoylation to human health is highlighted by the evidence linking dysregulated sumoylation to a variety of human diseases, including cancer, diabetes, heart disease, and neurodegenerative disorders such as Alzheimer, Parkinson, and Huntington diseases. The goal of the proposed research is to understand, at the molecular level, how sumoylation is controlled in normal physiology and how this process becomes dysregulated in disease states. The results of the proposed studies will provide fundamental information needed for the development of effective therapeutics to treat diverse human diseases in which protein sumoylation is disturbed.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM103613-02
Application #
8588945
Study Section
Special Emphasis Panel (ZRG1-CB-F (02))
Program Officer
Dunsmore, Sarah
Project Start
2012-12-01
Project End
2016-11-30
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
2
Fiscal Year
2014
Total Cost
$266,760
Indirect Cost
$95,760
Name
Emory University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
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