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Lysine ubiquitination and acetylation of human cardiac 20S proteasomes
Author(s) -
Zong Nobel,
Ping Peipei,
Lau Edward,
Choi Howard J. H.,
Ng Dominic C. M.,
Meyer David,
Fang Caiyun,
Li Haomin,
Wang Ding,
Zelaya Ivette M.,
Yates John R.,
Lam Maggie P. Y.
Publication year - 2014
Publication title -
proteomics – clinical applications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.948
H-Index - 54
eISSN - 1862-8354
pISSN - 1862-8346
DOI - 10.1002/prca.201400029
Subject(s) - ubiquitin , proteasome , crosstalk , acetylation , lysine , microbiology and biotechnology , cardiomyopathy , biology , computational biology , chemistry , biochemistry , medicine , heart failure , amino acid , gene , physics , optics
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.