Dissecting the molecular effects of cigarette smoke on proteasome function

Kammerl, Ilona; Caniard, Anne; Merl-Pham, Juliane; Ben‐Nissan, Gili; Mayr, Christoph H.; Mossina, Alessandra; Geerlof, Arie; Eickelberg, Oliver; Hauck, Stefanie M.; Sharon, Michal; Meiners, Silke

doi:10.1016/j.jprot.2018.12.015

Cited by 14 publications

(19 citation statements)

References 56 publications

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“…Small subpopulations of non-acetylated proteoforms could also be detected for most of the subunits. The mammalian PSMA3 subunit was also singly phosphorylated, as reported earlier 72,73 . However, this subunit was not detected at all for the yeast complex.…”

Section: Identification Of a New Psma7 Proteoformsupporting

confidence: 68%

Comparative structural analysis of 20S proteasome ortholog protein complexes by native mass spectrometry

Vimer¹,

Nissan²,

Morgenstern³

et al. 2020

Preprint

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Ortholog protein complexes are responsible for equivalent functions in different organisms. However, during evolution, each organism adapts to meet its physiological needs and the environmental challenges imposed by its niche. This selection pressure leads to structural diversity in protein complexes, which are often difficult to specify, especially in the absence of high-resolution structures. Here, we describe a multi-level experimental approach based on native mass spectrometry (MS) tools for elucidating the structural preservation and variations among highly related protein complexes. The 20S proteasome, an essential protein degradation machinery, served as our model system, wherein we examined five complexes isolated from different organisms. We show that throughout evolution, from the T. acidophilum archaeal prokaryotic complex to the eukaryotic 20S proteasomes in yeast (S. cerevisiae) and mammals (rat - R. norvegicus, rabbit - O. cuniculus and human - HEK293 cells), the proteasome increased both in size and stability. Native Ms structural signatures of the rat and rabbit 20S proteasomes, which heretofore lacked high-resolution three-dimensional structures, highly resembled that of the human complex. Using cryo-electron microscopy single-particle analysis we were able to obtain a high-resolution structure of the rat 20S proteasome, allowing us to validate the MS-based results. Our study also revealed that the yeast complex, and not those in mammals, was the largest in size, and displayed the greatest degree of kinetic stability. Moreover, we also identified a new proteoform of the <a></a><a>PSMA7 </a>subunit that resides within the rat and rabbit complexes, which to our knowledge have not been previously described. Altogether, our strategy enables elucidation of the unique structural properties of protein complexes that are highly similar to one another, a framework that is valid not only to ortholog protein complexes, but also for other highly related protein assemblies.

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Section: Identification Of a New Psma7 Proteoformsupporting

confidence: 68%

Comparative structural analysis of 20S proteasome ortholog protein complexes by native mass spectrometry

Vimer¹,

Nissan²,

Morgenstern³

et al. 2020

Preprint

Self Cite

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“…Disposal of non-wanted 26S proteasomes is mediated by autophagosomal proteaphagy as mentioned above for the 20S proteasome (Cohen- Kaplan et al, 2016;Cohen-Kaplan, Ciechanover, & Livneh, 2017;Livneh et al, 2016). In addition, disassembly of the 26S pro teasome takes place under conditions of oxidative stress (Livnat- Segref et al, 2014;Yu et al, 2019) or cigarette smoke (Kammerl et al, 2019) possibly due to posttranslational modifications that disrupt 19S and 20S interacting interfaces (see below). Inhibition of 26S activity may also be mediated by interaction with oligomeric proteins such as tau or mutant huntingtin smiliar to the above described effects on the 20S proteasome (Bennett et al, 2005;Hipp et al, 2012;Myeku et al, 2016).…”

Section: Regulation Of 26s Proteasome Formation and Assemblymentioning

confidence: 97%

Exploring the proteasome system: A novel concept of proteasome inhibition and regulation

Wang

Meul

Meiners

2020

Pharmacology & Therapeutics

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“…Similarly, we recently observed that immunoproteasome activity is activated in peripheral blood mononuclear cells (PBMCs) of patients with severe chronic obstructive pulmonary diseases (COPD), a major tobacco smoke related lung disease [ 25 ]. In contrast, proteasome and immunoproteasome function were inhibited in lungs of patients with severe COPD [ 26 , 27 ] and by exposure to cigarette smoke in vitro and in vivo [ 26 , 28 , 29 , 30 ]. Immunoproteasome dysfunction is also a feature of cardiovascular diseases such as dilated cardiomyopathy, cardiac failure, and atherosclerosis and has been correlated with disease progression [ 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

Blood Immunoproteasome Activity Is Regulated by Sex, Age and in Chronic Inflammatory Diseases: A First Population-Based Study

Kammerl

Flexeder

Karrasch

et al. 2021

Cells

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Dysfunction of the immunoproteasome has been implicated in cardiovascular and pulmonary diseases. Its potential as a biomarker for predicting disease stages, however, has not been investigated so far and population-based analyses on the impact of sex and age are missing. We here analyzed the activity of all six catalytic sites of the proteasome in isolated peripheral blood mononuclear cells obtained from 873 study participants of the KORA FF4 study using activity-based probes. The activity of the immuno- and standard proteasome correlated clearly with elevated leukocyte counts of study participants. Unexpectedly, we observed a strong sex dimorphism for proteasome activity with significantly lower immunoproteasome activity in women. In aging, almost all catalytic activities of the proteasome were activated in aged women while maintained upon aging in men. We also noted distinct sex-related activation patterns of standard and immunoproteasome active sites in chronic inflammatory diseases such as diabetes, cardiovascular diseases, asthma, or chronic obstructive pulmonary disease as determined by multiple linear regression modeling. Our data thus provides a conceptual framework for future analysis of immunoproteasome function as a bio-marker for chronic inflammatory disease development and progression.

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Dissecting the molecular effects of cigarette smoke on proteasome function

Cited by 14 publications

References 56 publications

Comparative structural analysis of 20S proteasome ortholog protein complexes by native mass spectrometry

Comparative structural analysis of 20S proteasome ortholog protein complexes by native mass spectrometry

Exploring the proteasome system: A novel concept of proteasome inhibition and regulation

Blood Immunoproteasome Activity Is Regulated by Sex, Age and in Chronic Inflammatory Diseases: A First Population-Based Study

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