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In Vivo Detection and Analysis of Rb Protein SUMOylation in Human Cells
Published on: November 2, 2017
Comparative proteomic analysis identifies a role for SUMO in protein quality control
Michael H Tatham1, Ivan Matic, Matthias Mann
1Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.
Science Signaling
|June 23, 2011
Summary
Small ubiquitin-like modifiers (SUMOs) play crucial roles in cellular functions. Proteasome inhibition increases SUMO conjugation, suggesting SUMOs have roles beyond protein degradation, particularly in response to misfolded proteins.
Area of Science:
- Cellular Biology
- Molecular Biology
- Posttranslational Modifications
Background:
- Small ubiquitin-like modifiers (SUMOs) regulate protein function through covalent modification, impacting gene transcription, cell cycle, and DNA repair.
- SUMOylation and ubiquitination are generally independent but both increase upon proteasome inhibition.
- The precise relationship between SUMOylation and proteasomal degradation remains incompletely understood.
Purpose of the Study:
- To investigate the relationship between SUMOylation and proteasomal degradation.
- To identify SUMO-2 substrates under proteasome inhibition.
- To elucidate the role of SUMOylation in cellular responses to proteotoxic stress.
Main Methods:
- Quantitative proteomic analysis of SUMO-2 substrates.
- Inhibition of the proteasome using MG132.
- Comparison with SUMOylation changes induced by heat stress.
Main Results:
- Proteasome inhibition with MG132 led to increased SUMO-2 conjugation, dependent on protein synthesis, suggesting a response to newly synthesized, misfolded proteins.
- Heat stress and MG132 treatment showed parallels in SUMO-2 subproteome changes.
- Proteasomal inhibition caused accumulation of conjugated SUMO paralogs in insoluble inclusions and K63-linked polyubiquitin chains on SUMO-2 substrates.
Conclusions:
- SUMOylation is involved in the cellular response to accumulating misfolded proteins, independent of direct proteasomal degradation pathways.
- The findings suggest novel, proteasome-independent functions for SUMOs in managing protein misfolding.
- SUMO paralogs and specific ubiquitin chain linkages accumulate in insoluble aggregates during proteasomal stress.
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