Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
9.4
4.8
Journals
Biomolecules
Special Issues
Looking Back and Ahead: Emerging Concepts in Ubiquitin and UBLs
share announcement

Looking Back and Ahead: Emerging Concepts in Ubiquitin and UBLs

A special issue of Biomolecules (ISSN 2218-273X).

Deadline for manuscript submissions: closed (15 February 2021) | Viewed by 35458

Special Issue Editors

Dr. Dmitris Xirodimas

E-Mail Website
Guest Editor
CRBM, CNRS, University of Montpellier, UMR5237, Montpellier CEDEX 5, France
Interests: ubiquitin-like molecules; cell growth regulation
Special Issues, Collections and Topics in MDPI journals
Dr. Elena Santonico

E-Mail Website
Guest Editor
Department of Biology, University of Rome Tor Vergata, Via della ricerca scientifica, 00133 Rome, Italy
Interests: ubiquitin-like molecules; cell growth regulation

Special Issue Information

Dear Colleagues,

Post-translational modification by ubiquitin and ubiquitin-like (UBL) modifiers plays a crucial role in cellular signal transduction, by controlling function, localization, and interactions of a large number of proteins. Both the conjugation of ubiquitin and UBLs occurs through the sequential action of three enzymes, called activating enzyme (E1), conjugating enzyme (E2), and ligase (E3). It has been ascertained that this machinery generates different profiles of protein modification, each having a specific functional outcome. Indeed, while ubiquitin chains were initially described as a signal for proteasomal degradation, nondegradative ubiquitination has proved to be a key modification in endocytosis, histone modifications, transcriptional regulation, and kinase signaling. Likewise, the conjugation of UBLs like NEDD8 and SUMO has proven to be a key node in distinct regulatory networks, such as the regulation of the immune system, cell cycle control, and cell death. Notably, SUMO and NEDD8 also form chains; moreover, SUMO chains can be targeted for ubiquitination, and ubiquitin can be subjected to neddylation and sumoylation. The functional role of these covalent modifications primarily depends on their recognition by receptors containing binding domains that dictate the formation of noncovalent protein complexes driving the specificity of the signal transduction process. Dysfunction within these mechanisms leads to severe pathological conditions, among them neurodegenerative diseases and cancers.

The central role of ubiquitin and UBLs in such diverse cellular processes makes them attractive targets for selective drug discovery. This issue aims to enlighten researchers on progress regarding the new functions and regulatory roles of ubiquitin and UBLs.

Prof. Dmitris Xirodimas
Dr. Elena Santonico
Guest Editors

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. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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

  • ubiquitin
  • ubiquitin-like (UBL)
  • post-translational modification (PTM)
  • protein degradation
  • E1
  • E2
  • E3

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue policies can be found here.

Related Special Issue

Published Papers (6 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

Jump to: Review

19 pages, 6324 KiB  
Article
Inhibiting Neddylation with MLN4924 Suppresses Growth and Delays Multicellular Development in Dictyostelium discoideum
by Robert J. Huber, William D. Kim and Sabateeshan Mathavarajah
Biomolecules 2021, 11(3), 482; https://doi.org/10.3390/biom11030482 - 23 Mar 2021
Cited by 3 | Viewed by 3538
Abstract
Neddylation is a post-translational modification that is essential for a variety of cellular processes and is linked to many human diseases including cancer, neurodegeneration, and autoimmune disorders. Neddylation involves the conjugation of the ubiquitin-like modifier neural precursor cell expressed developmentally downregulated protein 8 [...] Read more.
Neddylation is a post-translational modification that is essential for a variety of cellular processes and is linked to many human diseases including cancer, neurodegeneration, and autoimmune disorders. Neddylation involves the conjugation of the ubiquitin-like modifier neural precursor cell expressed developmentally downregulated protein 8 (NEDD8) to target proteins, and has been studied extensively in various eukaryotes including fungi, plants, and metazoans. Here, we examine the biological processes influenced by neddylation in the social amoeba, Dictyostelium discoideum, using a well-established inhibitor of neddylation, MLN4924 (pevonedistat). NEDD8, and the target of MLN4924 inhibition, NEDD8-activating enzyme E1 (NAE1), are highly conserved in D. discoideum (Nedd8 and Nae1, respectively). Treatment of D. discoideum cells with MLN4924 increased the amount of free Nedd8, suggesting that MLN4924 inhibited neddylation. During growth, MLN4924 suppressed cell proliferation and folic acid-mediated chemotaxis. During multicellular development, MLN4924 inhibited cyclic adenosine monophosphate (cAMP)-mediated chemotaxis, delayed aggregation, and suppressed fruiting body formation. Together, these findings indicate that neddylation plays an important role in regulating cellular and developmental events during the D. discoideum life cycle and that this organism can be used as a model system to better understand the essential roles of neddylation in eukaryotes, and consequently, its involvement in human disease. Full article
(This article belongs to the Special Issue Looking Back and Ahead: Emerging Concepts in Ubiquitin and UBLs)
►▼ Show Figures

Figure 1

16 pages, 3720 KiB  
Article
The Arg/N-Degron Pathway—A Potential Running Back in Fine-Tuning the Inflammatory Response?
by Dominique Leboeuf, Maxim Pyatkov, Timofei S. Zatsepin and Konstantin Piatkov
Biomolecules 2020, 10(6), 903; https://doi.org/10.3390/biom10060903 - 14 Jun 2020
Cited by 7 | Viewed by 5106
Abstract
Recognition of danger signals by a cell initiates a powerful cascade of events generally leading to inflammation. Inflammatory caspases and several other proteases become activated and subsequently cleave their target proinflammatory mediators. The irreversible nature of this process implies that the newly generated [...] Read more.
Recognition of danger signals by a cell initiates a powerful cascade of events generally leading to inflammation. Inflammatory caspases and several other proteases become activated and subsequently cleave their target proinflammatory mediators. The irreversible nature of this process implies that the newly generated proinflammatory fragments need to be sequestered, inhibited, or degraded in order to cancel the proinflammatory program or prevent chronic inflammation. The Arg/N-degron pathway is a ubiquitin-dependent proteolytic pathway that specifically degrades protein fragments bearing N-degrons, or destabilizing residues, which are recognized by the E3 ligases of the pathway. Here, we report that the Arg/N-degron pathway selectively degrades a number of proinflammatory fragments, including some activated inflammatory caspases, contributing in tuning inflammatory processes. Partial ablation of the Arg/N-degron pathway greatly increases IL-1β secretion, indicating the importance of this ubiquitous pathway in the initiation and resolution of inflammation. Thus, we propose a model wherein the Arg/N-degron pathway participates in the control of inflammation in two ways: in the generation of inflammatory signals by the degradation of inhibitory anti-inflammatory domains and as an “off switch” for inflammatory responses through the selective degradation of proinflammatory fragments. Full article
(This article belongs to the Special Issue Looking Back and Ahead: Emerging Concepts in Ubiquitin and UBLs)
►▼ Show Figures

Figure 1

Review

Jump to: Research

21 pages, 1752 KiB  
Review
Highly Specialized Ubiquitin-Like Modifications: Shedding Light into the UFM1 Enigma
by Katharina F. Witting and Monique P.C. Mulder
Biomolecules 2021, 11(2), 255; https://doi.org/10.3390/biom11020255 - 10 Feb 2021
Cited by 23 | Viewed by 5436
Abstract
Post-translational modification with Ubiquitin-like proteins represents a complex signaling language regulating virtually every cellular process. Among these post-translational modifiers is Ubiquitin-fold modifier (UFM1), which is covalently attached to its substrates through the orchestrated action of a dedicated enzymatic cascade. Originally identified to be [...] Read more.
Post-translational modification with Ubiquitin-like proteins represents a complex signaling language regulating virtually every cellular process. Among these post-translational modifiers is Ubiquitin-fold modifier (UFM1), which is covalently attached to its substrates through the orchestrated action of a dedicated enzymatic cascade. Originally identified to be involved embryonic development, its biological function remains enigmatic. Recent research reveals that UFM1 regulates a variety of cellular events ranging from DNA repair to autophagy and ER stress response implicating its involvement in a variety of diseases. Given the contribution of UFM1 to numerous pathologies, the enzymes of the UFM1 cascade represent attractive targets for pharmacological inhibition. Here we discuss the current understanding of this cryptic post-translational modification especially its contribution to disease as well as expand on the unmet needs of developing chemical and biochemical tools to dissect its role. Full article
(This article belongs to the Special Issue Looking Back and Ahead: Emerging Concepts in Ubiquitin and UBLs)
►▼ Show Figures

Graphical abstract

13 pages, 1376 KiB  
Review
Breakdown of Filamentous Myofibrils by the UPS–Step by Step
by Dina Aweida and Shenhav Cohen
Biomolecules 2021, 11(1), 110; https://doi.org/10.3390/biom11010110 - 15 Jan 2021
Cited by 14 | Viewed by 6940
Abstract
Protein degradation maintains cellular integrity by regulating virtually all biological processes, whereas impaired proteolysis perturbs protein quality control, and often leads to human disease. Two major proteolytic systems are responsible for protein breakdown in all cells: autophagy, which facilitates the loss of organelles, [...] Read more.
Protein degradation maintains cellular integrity by regulating virtually all biological processes, whereas impaired proteolysis perturbs protein quality control, and often leads to human disease. Two major proteolytic systems are responsible for protein breakdown in all cells: autophagy, which facilitates the loss of organelles, protein aggregates, and cell surface proteins; and the ubiquitin-proteasome system (UPS), which promotes degradation of mainly soluble proteins. Recent findings indicate that more complex protein structures, such as filamentous assemblies, which are not accessible to the catalytic core of the proteasome in vitro, can be efficiently degraded by this proteolytic machinery in systemic catabolic states in vivo. Mechanisms that loosen the filamentous structure seem to be activated first, hence increasing the accessibility of protein constituents to the UPS. In this review, we will discuss the mechanisms underlying the disassembly and loss of the intricate insoluble filamentous myofibrils, which are responsible for muscle contraction, and whose degradation by the UPS causes weakness and disability in aging and disease. Several lines of evidence indicate that myofibril breakdown occurs in a strictly ordered and controlled manner, and the function of AAA-ATPases is crucial for their disassembly and loss. Full article
(This article belongs to the Special Issue Looking Back and Ahead: Emerging Concepts in Ubiquitin and UBLs)
►▼ Show Figures

Figure 1

22 pages, 1142 KiB  
Review
Ubiquitomics: An Overview and Future
by George Vere, Rachel Kealy, Benedikt M. Kessler and Adan Pinto-Fernandez
Biomolecules 2020, 10(10), 1453; https://doi.org/10.3390/biom10101453 - 17 Oct 2020
Cited by 28 | Viewed by 7468
Abstract
Covalent attachment of ubiquitin, a small globular polypeptide, to protein substrates is a key post-translational modification that determines the fate, function, and turnover of most cellular proteins. Ubiquitin modification exists as mono- or polyubiquitin chains involving multiple ways how ubiquitin C-termini are connected [...] Read more.
Covalent attachment of ubiquitin, a small globular polypeptide, to protein substrates is a key post-translational modification that determines the fate, function, and turnover of most cellular proteins. Ubiquitin modification exists as mono- or polyubiquitin chains involving multiple ways how ubiquitin C-termini are connected to lysine, perhaps other amino acid side chains, and N-termini of proteins, often including branching of the ubiquitin chains. Understanding this enormous complexity in protein ubiquitination, the so-called ‘ubiquitin code’, in combination with the ∼1000 enzymes involved in controlling ubiquitin recognition, conjugation, and deconjugation, calls for novel developments in analytical techniques. Here, we review different headways in the field mainly driven by mass spectrometry and chemical biology, referred to as “ubiquitomics”, aiming to understand this system’s biological diversity. Full article
(This article belongs to the Special Issue Looking Back and Ahead: Emerging Concepts in Ubiquitin and UBLs)
►▼ Show Figures

Figure 1

21 pages, 2055 KiB  
Review
Old and New Concepts in Ubiquitin and NEDD8 Recognition
by Elena Santonico
Biomolecules 2020, 10(4), 566; https://doi.org/10.3390/biom10040566 - 7 Apr 2020
Cited by 22 | Viewed by 5948
Abstract
Post-translational modifications by ubiquitin and ubiquitin-like proteins (Ubls) have known roles in a myriad of cellular processes. Ubiquitin- and Ubl-binding domains transmit the information conferred by these post-translational modifications by recognizing functional surfaces and, when present, different chain structures. Numerous domains binding to [...] Read more.
Post-translational modifications by ubiquitin and ubiquitin-like proteins (Ubls) have known roles in a myriad of cellular processes. Ubiquitin- and Ubl-binding domains transmit the information conferred by these post-translational modifications by recognizing functional surfaces and, when present, different chain structures. Numerous domains binding to ubiquitin have been characterized and their structures solved. Analogously, motifs selectively interacting with SUMO (small ubiquitin-like modifier) have been identified in several proteins and their role in SUMO-dependent processes investigated. On the other hand, proteins that specifically recognize other Ubl modifications are known only in a few cases. The high sequence identity between NEDD8 and ubiquitin has made the identification of specific NEDD8-binding domains further complicated due to the promiscuity in the recognition by several ubiquitin-binding domains. Two evolutionarily related domains, called CUBAN (cullin-binding domain associating with NEDD8) and CoCUN (cousin of CUBAN), have been recently described. The CUBAN binds monomeric NEDD8 and neddylated cullins, but it also interacts with di-ubiquitin chains. Conversely, the CoCUN domain only binds ubiquitin. CUBAN and CoCUN provide an intriguing example of how nature solved the issue of promiscuity versus selectivity in the recognition of these two highly related molecules. The structural information available to date suggests that the ancestor of CUBAN and CoCUN was a three-helix bundle domain that diversified in KHNYN (KH and NYN domain-containing) and N4BP1 (NEDD4-binding protein-1) by acquiring different features. Indeed, these domains diverged towards two recognition modes, that recall respectively the electrostatic interaction utilized by the E3-ligase RBX1/2 in the interaction with NEDD8, and the hydrophobic features described in the recognition of ubiquitin by CUE (coupling ubiquitin conjugation to ER degradation) domains. Intriguingly, CUBAN and CoCUN domains are only found in KHNYN and N4BP1, respectively, both proteins belonging to the PRORP family whose members are characterized by the combination of protein modules involved in RNA metabolism with domains mediating ubiquitin/NEDD8 recognition. This review recapitulates the current knowledge and recent findings of CUBAN and CoCUN domains and the proteins containing them. Full article
(This article belongs to the Special Issue Looking Back and Ahead: Emerging Concepts in Ubiquitin and UBLs)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-6
Back to TopTop