Lysine ubiquitination and acetylation of human cardiac 20S proteasomes

Zong, Nobel; Ping, Peipei; Lau, Edward; Choi, Howard; Ng, Dominic C. M.; Meyer, David W.; Fang, Changming; Li, Haomin; Wang, Ding; Zelaya, Ivette; Lam, Maggie P. Y.

doi:10.1002/prca.201400029

Cited by 14 publications

(11 citation statements)

References 22 publications

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“…Within the human cardiac 20S proteasomes, there are 63 Lys that are ubiquitinated lysines and 65 acetylated Lys, with approximately two thirds (or 39) of them shared. 291 Desmin, an intermediate filament protein involved in the alignment of mitochondria with the nucleus, myofilament, and the cell membrane, undergoes glycogen synthase kinase-3β phosphorylation in many models of heart failure, which alters its susceptibility to selective proteolysis and subsequent amyloid formation. 292 The extent of phosphorylation and proteolysis is decreased with cardiac resynchronization therapy, which also reveals a reduction of amyloid-like oligomer deposits.…”

Section: Proteomics and Ptmsmentioning

confidence: 99%

Assessing Cardiac Metabolism

Taegtmeyer¹,

Young²,

Lopaschuk³

et al. 2016

Circulation Research

230

147

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In a complex system of interrelated reactions, the heart converts chemical energy to mechanical energy. Energy transfer is achieved through coordinated activation of enzymes, ion channels, and contractile elements, as well as structural and membrane proteins. The heart’s needs for energy are difficult to overestimate. At a time when the cardiovascular research community is discovering a plethora of new molecular methods to assess cardiac metabolism, the methods remain scattered in the literature. The present statement on “Assessing Cardiac Metabolism” seeks to provide a collective and curated resource on methods and models used to investigate established and emerging aspects of cardiac metabolism. Some of those methods are refinements of classic biochemical tools, whereas most others are recent additions from the powerful tools of molecular biology. The aim of this statement is to be useful to many and to do justice to a dynamic field of great complexity.

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Section: Proteomics and Ptmsmentioning

confidence: 99%

Assessing Cardiac Metabolism

Taegtmeyer¹,

Young²,

Lopaschuk³

et al. 2016

Circulation Research

230

147

View full text Add to dashboard Cite

show abstract

“…74 Abundant examples in the literature are available, including a special issue on cardiovascular disease that focused on clinical and translational proteomics. [75][76][77][78][79][80][81][82][83][84][85][86][87] One specific example is activity-based protein profiling with proteomic techniques, which is currently being used to annotate the enzymatic proteome and uses chemical probes that target large groups of enzymes that have similar active-site features. 88 Contributing to the posttranscriptional complexity of the proteome are alternative splicing and isoform variants, often with extensive peptide redundancies, that are not easily addressed by standard rules of parsimony when acquired in the context of multidimensional quantitative proteomic studies.…”

Section: The Promise Of Proteomicsmentioning

confidence: 99%

Transformative Impact of Proteomics on Cardiovascular Health and Disease

Lindsey¹,

Mayr²,

Gomes³

et al. 2015

Circulation

142

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Abstract-The year 2014 marked the 20th anniversary of the coining of the term proteomics. The purpose of this scientific statement is to summarize advances over this period that have catalyzed our capacity to address the experimental, translational, and clinical implications of proteomics as applied to cardiovascular health and disease and to evaluate the current status of the field. Key successes that have energized the field are delineated; opportunities for proteomics to drive basic science research, facilitate clinical translation, and establish diagnostic and therapeutic healthcare algorithms are discussed; and challenges that remain to be solved before proteomic technologies can be readily translated from scientific discoveries to meaningful advances in cardiovascular care are addressed. Proteomics is the result of disruptive technologies, namely, mass spectrometry and database searching, which drove protein analysis from 1 protein at a time to protein mixture analyses that enable large-scale analysis of proteins and facilitate paradigm shifts in biological concepts that address important clinical questions. Over the past 20 years, the field of proteomics has matured, yet it is still developing rapidly. The scope of this statement will extend beyond the reaches of a typical review article and offer guidance on the use of next-generation proteomics for future scientific discovery in the basic research laboratory and clinical settings.

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“…It should be pointed out that a significant overlap between the ubiquitination and acetylation sites has been observed in human cardiac 20S proteasomes [ 39 ]. This crosstalk between acetylation, ubiquitination, and succinylation of proteasomal proteins may permit potential crosstalk in the regulation of proteasome functions.…”

Section: Resultsmentioning

confidence: 99%

Post-Translational Modifications of Extracellular Proteasome

et al. 2020

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The ubiquitin-proteasome system (UPS) is one of the major protein degradation pathways in eukaryotic cells. Abnormal functioning of this system has been observed in cancer and neurological diseases. The 20S proteasomes, essential components of the UPS, are present not only within the cells but also in the extracellular space, and their concentration in blood plasma has been found to be elevated and dependent upon the disease state, being of prognostic significance in patients suffering from cancer, liver diseases, and autoimmune diseases. However, functions of extracellular proteasomes and mechanisms of their release by cells remain largely unknown. The main mechanism of proteasome activity regulation is provided by modulation of their composition and post-translational modifications (PTMs). Moreover, diverse PTMs of proteins are known to participate in the loading of specific elements into extracellular vesicles. Since previous studies have revealed that the transport of extracellular proteasomes may occur via extracellular vesicles, we have set out to explore the PTMs of extracellular proteasomes in comparison to cellular counterparts. In this work, cellular and extracellular proteasomes were affinity purified and separated by SDS-PAGE for subsequent trypsinization and matrix-assisted laser desorption/ionization (MALDI) Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry (MS) analysis. In total, we could identify 64 and 55 PTM sites in extracellular and cellular proteasomes, respectively, including phosphorylation, ubiquitination, acetylation, and succinylation. We observed novel sites of acetylation at K238 and K192 of the proteasome subunits β2 and β3, respectively, that are specific for extracellular proteasomes. Moreover, cellular proteasomes show specific acetylation at K227 of α2 and ubiquitination at K201 of β3. Interestingly, succinylation of β6 at the residue K228 seems not to be present exclusively in extracellular proteasomes, whereas both extracellular and cellular proteasomes may also be acetylated at this site. The same situation takes place at K201 of the β3 subunit where ubiquitination is seemingly specific for cellular proteasomes. Moreover, crosstalk between acetylation, ubiquitination, and succinylation has been observed in the subunit α3 of both proteasome populations. These data will serve as a basis for further studies, aimed at dissection of the roles of extracellular proteasome-specific PTMs in terms of the function of these proteasomes and mechanism of their transport into extracellular space.

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Lysine ubiquitination and acetylation of human cardiac 20S proteasomes

Cited by 14 publications

References 22 publications

Assessing Cardiac Metabolism

Assessing Cardiac Metabolism

Transformative Impact of Proteomics on Cardiovascular Health and Disease

Post-Translational Modifications of Extracellular Proteasome

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