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Proteome dynamics and proteome function of cardiac 19S proteasomes.
- Source :
-
Molecular & cellular proteomics : MCP [Mol Cell Proteomics] 2011 May; Vol. 10 (5), pp. M110.006122. Date of Electronic Publication: 2011 Feb 25. - Publication Year :
- 2011
-
Abstract
- Myocardial proteasomes are comprised of 20S core particles and 19S regulatory particles, which together carry out targeted degradation of cardiac proteins. The 19S complex is unique among the regulators of proteasomes in that it affects both the capacity and specificity of protein degradation. However, a comprehensive molecular characterization of cardiac 19S complexes is lacking. In this investigation, we tailored a multidimensional chromatography-based purification strategy to isolate structurally intact and functionally viable 19S complexes from murine hearts. Two distinct subpopulations of 19S complexes were isolated based upon (1) potency of activating 20S proteolytic activity, and (2) molecular composition using a combination of immuno-detection, two-dimensional-differential gel electrophoresis, and MS-based approaches. Heat shock protein 90 (Hsp90) was identified to be characteristic to 19S subpopulation I. The physical interaction of Hsp90 with 19S complexes was demonstrated via multiple approaches. Inhibition of Hsp90 activity using geldanamycin or BIIB021 potentiated the ability of subpopulation I to activate 20S proteasomes in the murine heart, thus demonstrating functional specificity of Hsp90 in subpopulation I. This investigation has advanced our understanding of the molecular heterogeneity of cardiac proteasomes by identifying molecularly and functionally distinct cardiac 19S complexes. The preferential association of Hsp90 with 19S subpopulation I unveils novel targets for designing proteasome-based therapeutic interventions for combating cardiac disease.
- Subjects :
- Amino Acid Sequence
Animals
Chromatography, Liquid
Enzyme Activation
HSP90 Heat-Shock Proteins metabolism
Male
Mice
Mice, Inbred ICR
Molecular Sequence Data
Proteasome Endopeptidase Complex chemistry
Proteasome Endopeptidase Complex isolation & purification
Tandem Mass Spectrometry
Myocardium metabolism
Proteasome Endopeptidase Complex metabolism
Proteome metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1535-9484
- Volume :
- 10
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Molecular & cellular proteomics : MCP
- Publication Type :
- Academic Journal
- Accession number :
- 21357515
- Full Text :
- https://doi.org/10.1074/mcp.M110.006122