Lysine Ubiquitination and Acetylation of Human Cardiac 20S Proteasomes

Overview

Journal Proteomics Clin Appl

Specialty Biochemistry

Date 2014 Jun 25

PMID 24957502

Citations 9

Authors

Nobel Zong

Peipei Ping

Edward Lau

Howard Jh Choi

Dominic Cm Ng

David Meyer

Caiyun Fang

Haomin Li

Ding Wang

Ivette M Zelaya

John R Yates 3rd

Maggie Py Lam

Affiliations

Soon will be listed here.

Abstract

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.

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