title: Lysine ubiquitination and acetylation of human cardiac 20S proteasomes.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors: The NHLBI Proteomics Center at UCLA, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.|Departments of Physiology and Medicine/Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors: Nobel
authors: N
authors: Zong
authors: The NHLBI Proteomics Center at UCLA, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.|Departments of Physiology and Medicine/Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors: Peipei
authors: P
authors: Ping
authors: The NHLBI Proteomics Center at UCLA, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.|Departments of Physiology and Medicine/Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors: Edward
authors: E
authors: Lau
authors: The NHLBI Proteomics Center at UCLA, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors: Howard Jh
authors: HJ
authors: Choi
authors: The NHLBI Proteomics Center at UCLA, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors: Dominic Cm
authors: DC
authors: Ng
authors: The NHLBI Proteomics Center at UCLA, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors: David
authors: D
authors: Meyer
authors: The NHLBI Proteomics Center at UCLA, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors: Caiyun
authors: C
authors: Fang
authors: The NHLBI Proteomics Center at UCLA, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors: Haomin
authors: H
authors: Li
authors: The NHLBI Proteomics Center at UCLA, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.|Departments of Physiology and Medicine/Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors: Ding
authors: D
authors: Wang
authors: The NHLBI Proteomics Center at UCLA, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors: Ivette M
authors: IM
authors: Zelaya
authors: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA.
authors: John R
authors: JR
authors: Yates
authors: The NHLBI Proteomics Center at UCLA, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.|Departments of Physiology and Medicine/Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors: Maggie Py
authors: MP
authors: Lam
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009206:Myocardium / Q000201:enzymology*; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D054875:Ubiquitination
chemical_list: D046988:Proteasome Endopeptidase Complex; D008239:Lysine
keywords: 20S proteasome; Acetylation; PTM; Spectral library; Ubiquitination