Key result
High-resolution mass spectrometry identifies 39 shared ubiquitination and acetylation sites on human cardiac 20S proteasomes.
This study provides a comprehensive characterization of cardiac proteasome ubiquitination and acetylation sites, revealing significant overlap that suggests potential crosstalk in regulating proteasome functions in ischemic cardiomyopathy.
Hypothesis-generating for proteasome regulation in cardiomyopathy; leaves open functional crosstalk of shared sites and requires human validation.
PURPOSE: Altered proteasome functions are associated with multiple cardiomyopathies. While the proteasome targets polyubiquitinated proteins for destruction, it itself is modifiable by ubiquitination. We aim to identify the exact ubiquitination sites on cardiac proteasomes and examine whether they are also subject to acetylations. EXPERIMENTAL DESIGN: Assembled cardiac 20S proteasome complexes were purified from five human hearts with ischemic cardiomyopathy, then analyzed by high-resolution MS to identify ubiquitination and acetylation sites. We developed a library search strategy that may be used to complement database search in identifying PTM in different samples. RESULTS: We identified 63 ubiquitinated lysines from intact human cardiac 20S proteasomes. In parallel, 65 acetylated residues were also discovered, 39 of which shared with ubiquitination sites. CONCLUSION AND CLINICAL RELEVANCE: This is the most comprehensive characterization of cardiac proteasome ubiquitination to date. There are significant overlaps between the discovered ubiquitination and acetylation sites, permitting potential crosstalk in regulating proteasome functions. The information presented here will aid future therapeutic strategies aimed at regulating the functions of cardiac proteasomes.
No takes yet. Share an insight, caveat, or question.
Zong et al. (2014) studied Ischemic cardiomyopathy (n=5). High-resolution mass spectrometry analysis was evaluated on Identification of ubiquitination and acetylation sites on cardiac proteasomes. High-resolution mass spectrometry identified 63 ubiquitinated lysines and 65 acetylated residues from intact human cardiac 20S proteasomes, with 39 sites shared between the two modifications.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: