These authors have contributed equally to this study.
Lysine ubiquitination and acetylation of human cardiac 20S proteasomes
Version of Record online: 15 AUG 2014
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PROTEOMICS - Clinical Applications
Special Issue: Cardiovascular Disease: Clinical and Translational Proteomics
Volume 8, Issue 7-8, pages 590–594, August 2014
How to Cite
Zong, N., Ping, P., Lau, E., Choi, H. J. H., Ng, D. C. M., Meyer, D., Fang, C., Li, H., Wang, D., Zelaya, I. M., Yates, J. R. and Lam, M. P. Y. (2014), Lysine ubiquitination and acetylation of human cardiac 20S proteasomes. Prot. Clin. Appl., 8: 590–594. doi: 10.1002/prca.201400029
- Issue online: 15 AUG 2014
- Version of Record online: 15 AUG 2014
- Accepted manuscript online: 23 JUN 2014 07:59AM EST
- Manuscript Accepted: 10 JUN 2014
- Manuscript Revised: 12 MAY 2014
- Manuscript Received: 24 MAR 2014
- NIH. Grant Numbers: HL-R37–63901, HHSN268201000035C
- Laubisch endowment to P. Ping
- AHA. Grant Numbers: 13POST14700031, 12PRE11610024
- 20S proteasome;
- Spectral library;
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.
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.
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.