Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.8
5.6
Journals
IJMS
Special Issues
Proteostasis and Proteasome Inhibitors 2.0
ijms-logo
Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Proteostasis and Proteasome Inhibitors 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (28 February 2021) | Viewed by 5979

Special Issue Editor

Prof. Dr. David M. Pereira

E-Mail Website
Guest Editor
Laboratory of Pharmacognosy, Faculty of Pharmacy, University of Porto, Porto, Portugal
Interests: natural products chemistry; bioactive small molecules; anti-inflammatory drugs; pro-apoptotic drugs; endoplasmic reticulum stress; proteasome inhibitors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

The function of proteins is largely affected by their tridimensional structure, nevertheless incorrect folding of proteins is an inevitable problem that is present in all eukaryotic organelles. Misfolded proteins often present reduced or even absent activity and can be the basis of several proteinopathies, including neurodegenerative diseases or even lysosomal storage disease. To prevent the aggregation of misfolded proteins, eukaryotic cells have evolved robust pathways that are often interconnected with compartmental protein quality control. These pathways detect misfolded proteins and action refolding into functional proteins using chaperones, sequestering them in large inclusions pathway proteins, small heat shock chaperone, or degrading them through the ubiquitin-proteasome system or autophagy. This special issue will be dedicated to all aspects of proteostasis, protein quality control pathways, and proteasome inhibitors.

Prof. Dr. David Pereira
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Proteostasis
  • Proteasome inhibitors
  • Proteotoxicity
  • Folding
  • Cancer
  • Lisosome storage diseases
  • Neurodegenerative diseases

Published Papers (2 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

18 pages, 3299 KiB  
Article
Yeast Rpn4 Links the Proteasome and DNA Repair via RAD52 Regulation
by Daria S. Spasskaya, Nonna I. Nadolinskaia, Vera V. Tutyaeva, Yuriy P. Lysov, Vadim L. Karpov and Dmitry S. Karpov
Int. J. Mol. Sci. 2020, 21(21), 8097; https://doi.org/10.3390/ijms21218097 - 30 Oct 2020
Cited by 4 | Viewed by 2905
Abstract
Environmental and intracellular factors often damage DNA, but multiple DNA repair pathways maintain genome integrity. In yeast, the 26S proteasome and its transcriptional regulator and substrate Rpn4 are involved in DNA damage resistance. Paradoxically, while proteasome dysfunction may induce hyper-resistance to DNA-damaging agents, [...] Read more.
Environmental and intracellular factors often damage DNA, but multiple DNA repair pathways maintain genome integrity. In yeast, the 26S proteasome and its transcriptional regulator and substrate Rpn4 are involved in DNA damage resistance. Paradoxically, while proteasome dysfunction may induce hyper-resistance to DNA-damaging agents, Rpn4 malfunction sensitizes yeasts to these agents. Previously, we proposed that proteasome inhibition causes Rpn4 stabilization followed by the upregulation of Rpn4-dependent DNA repair genes and pathways. Here, we aimed to elucidate the key Rpn4 targets responsible for DNA damage hyper-resistance in proteasome mutants. We impaired the Rpn4-mediated regulation of candidate genes using the CRISPR/Cas9 system and tested the sensitivity of mutant strains to 4-NQO, MMS and zeocin. We found that the separate or simultaneous deregulation of 19S or 20S proteasome subcomplexes induced MAG1, DDI1, RAD23 and RAD52 in an Rpn4-dependent manner. Deregulation of RAD23, DDI1 and RAD52 sensitized yeast to DNA damage. Genetic, epigenetic or dihydrocoumarin-mediated RAD52 repression restored the sensitivity of the proteasome mutants to DNA damage. Our results suggest that the Rpn4-mediated overexpression of DNA repair genes, especially RAD52, defines the DNA damage hyper-resistant phenotype of proteasome mutants. The developed yeast model is useful for characterizing drugs that reverse the DNA damage hyper-resistance phenotypes of cancers. Full article
(This article belongs to the Special Issue Proteostasis and Proteasome Inhibitors 2.0)
►▼ Show Figures

Graphical abstract

15 pages, 1608 KiB  
Article
Effect of Ferulic Acid, a Phenolic Inducer of Fungal Laccase, on 26S Proteasome Activities In Vitro
by Anita Swatek and Magdalena Staszczak
Int. J. Mol. Sci. 2020, 21(7), 2463; https://doi.org/10.3390/ijms21072463 - 02 Apr 2020
Cited by 9 | Viewed by 2636
Abstract
The 26S proteasome is an ATP-dependent protease complex (2.5 MDa) that degrades most cellular proteins in Eukaryotes, typically those modified by a polyubiquitin chain. The proteasome-mediated proteolysis regulates a variety of critical cellular processes such as transcriptional control, cell cycle, oncogenesis, apoptosis, protein [...] Read more.
The 26S proteasome is an ATP-dependent protease complex (2.5 MDa) that degrades most cellular proteins in Eukaryotes, typically those modified by a polyubiquitin chain. The proteasome-mediated proteolysis regulates a variety of critical cellular processes such as transcriptional control, cell cycle, oncogenesis, apoptosis, protein quality control, and stress response. Previous studies conducted in our laboratory have shown that 26S proteasomes are involved in the regulation of ligninolytic enzymes (such as laccase) in white-rot fungi in response to nutrient starvation, cadmium exposure, and ER stress. Laccases are useful biocatalysts for a wide range of biotechnological applications. The goal of the current study was to determine the effect of ferulic acid (4-hydroxy-3-methoxycinnamic acid), a phenolic compound known to induce some ligninolytic enzymes, on proteasomes isolated from mycelia of the wood-decomposing basidiomycete Trametes versicolor. The peptidase activities of 26S proteasomes were assayed by measuring the hydrolysis of fluorogenic peptide substrates specific for each active site: Suc-LLVY-AMC, Z-GGR-AMC and Z-LLE-AMC for chymotrypsin-like, trypsin-like, and caspase-like site, respectively. Ferulic acid affected all peptidase activities of the 26S fungal proteasomes in a concentration-dependent manner. A possible inhibitory effect of ferulic acid on peptidase activities of the 26S human proteasomes was tested as well. Moreover, the ability of ferulic acid to inhibit (at concentrations known to induce laccase activity in white-rot fungi) the rate of 26S proteasome-catalyzed degradation of a model full-length protein substrate (β-casein) was demonstrated by a fluorescamine assay and by a gel-electrophoretic analysis. Our findings provide new insights into the role of ferulic acid in lignin-degrading fungi. However, the detailed molecular mechanisms involved remain to be elucidated by future studies. Full article
(This article belongs to the Special Issue Proteostasis and Proteasome Inhibitors 2.0)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-2
Back to TopTop