Special Issue "Ubiquitination in Health and Disease"

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (31 December 2018)

Special Issue Editors

Guest Editor
Prof. Germana Meroni

Department of Life Sciences, University of Trieste, Via L. Giorgieri, 5, 34127, Trieste, Italy
Website | E-Mail
Interests: genetic diseases; TRIM E3 ubiquitin ligases; ubiquitination
Guest Editor
Dr. Giuseppe Merla

Division of Medical Genetics, IRCCS Casa Sollievo della Sofferenza, viale Cappuccini 71013 San Giovanni Rotondo (FG), Italy
Website | E-Mail
Interests: medical genetics; ubiquitination; autophagy

Special Issue Information

Dear Colleagues,

Ubiquitination is a post-translational modification process that controls the degradation, signaling and activity of many, if not all, cellular proteins. Ubiquitination needs to be finely tuned and is catalyzed and controlled by several players: ubiquitin; the E1 ubiquitin activating enzyme, the E2 ubiquitin conjugating enzymes, the E3 ubiquitin ligases, which compose the ubiquitination cascade; the deubiquitination enzymes that reverse the modification; and the proteins that recognize the ubiquitination code and translate the signal. Substrates can be modified with a single ubiquitin peptide, in one or multiple sites, or with a poly-ubiquitin chain. The topology of the built ubiquitin chain determines the fate of the targeted substrate. In cells also free poly-ubiquitin chains, which are not conjugated to any target protein, can be synthesized. In recent years, considerable progress has been made in the understanding the molecular action of ubiquitin in signaling pathways and how alterations in the ubiquitin system lead to the development of several human diseases from cancer, metabolic syndromes, neurodegenerative diseases, inflammatory disorders, and rare genetic disorders.

In this Special Issue of Cells, we invite your contributions, either in the form of original research articles or reviews addressing the expanding field of mechanistic and functional insights into the physiological and pathological role of specific ubiquitination pathways and components.

Prof. Germana Meroni
Dr. Giuseppe Merla
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 papers will be 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. Cells 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 1800 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
  • E3 ubiquitin ligases
  • proteasome
  • E2 ubiquitin conjugating enzymes
  • ubiquitin binding domains

Published Papers (8 papers)

View options order results:
result details:
Displaying articles 1-8
Export citation of selected articles as:

Research

Jump to: Review, Other

Open AccessFeature PaperArticle UBE2E1 Is Preferentially Expressed in the Cytoplasm of Slow-Twitch Fibers and Protects Skeletal Muscles from Exacerbated Atrophy upon Dexamethasone Treatment
Cells 2018, 7(11), 214; https://doi.org/10.3390/cells7110214
Received: 24 September 2018 / Revised: 9 November 2018 / Accepted: 13 November 2018 / Published: 16 November 2018
PDF Full-text (3736 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Skeletal muscle mass is reduced during many diseases or physiological situations (disuse, aging), which results in decreased strength and increased mortality. Muscle mass is mainly controlled by the ubiquitin-proteasome system (UPS), involving hundreds of ubiquitinating enzymes (E2s and E3s) that target their dedicated
[...] Read more.
Skeletal muscle mass is reduced during many diseases or physiological situations (disuse, aging), which results in decreased strength and increased mortality. Muscle mass is mainly controlled by the ubiquitin-proteasome system (UPS), involving hundreds of ubiquitinating enzymes (E2s and E3s) that target their dedicated substrates for subsequent degradation. We recently demonstrated that MuRF1, an E3 ubiquitin ligase known to bind to sarcomeric proteins (telethonin, α-actin, myosins) during catabolic situations, interacts with 5 different E2 enzymes and that these E2-MuRF1 couples are able to target telethonin, a small sarcomeric protein, for degradation. Amongst the E2s interacting with MuRF1, E2E1 was peculiar as the presence of the substrate was necessary for optimal MuRF1-E2E1 interaction. In this work, we focused on the putative role of E2E1 during skeletal muscle atrophy. We found that E2E1 expression was restricted to type I and type IIA muscle fibers and was not detectable in type IIB fibers. This strongly suggests that E2E1 targets are fiber-specific and may be strongly linked to the contractile and metabolic properties of the skeletal muscle. However, E2E1 knockdown was not sufficient for preserving the protein content in C2C12 myotubes subjected to a catabolic state (dexamethasone treatment), suggesting that E2E1 is not involved in the development of muscle atrophy. By contrast, E2E1 knockdown aggravated the atrophying process in both catabolic C2C12 myotubes and the Tibialis anterior muscle of mice, suggesting that E2E1 has a protective effect on muscle mass. Full article
(This article belongs to the Special Issue Ubiquitination in Health and Disease)
Figures

Figure 1

Open AccessArticle Drosophila HUWE1 Ubiquitin Ligase Regulates Endoreplication and Antagonizes JNK Signaling During Salivary Gland Development
Cells 2018, 7(10), 151; https://doi.org/10.3390/cells7100151
Received: 8 August 2018 / Revised: 20 September 2018 / Accepted: 21 September 2018 / Published: 26 September 2018
PDF Full-text (4062 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The HECT-type ubiquitin ligase HECT, UBA and WWE Domain Containing 1, (HUWE1) regulates key cancer-related pathways, including the Myc oncogene. It affects cell proliferation, stress and immune signaling, mitochondria homeostasis, and cell death. HUWE1 is evolutionarily conserved from Caenorhabditis elegance to Drosophila melanogaster
[...] Read more.
The HECT-type ubiquitin ligase HECT, UBA and WWE Domain Containing 1, (HUWE1) regulates key cancer-related pathways, including the Myc oncogene. It affects cell proliferation, stress and immune signaling, mitochondria homeostasis, and cell death. HUWE1 is evolutionarily conserved from Caenorhabditis elegance to Drosophila melanogaster and Humans. Here, we report that the Drosophila ortholog, dHUWE1 (CG8184), is an essential gene whose loss results in embryonic lethality and whose tissue-specific disruption establishes its regulatory role in larval salivary gland development. dHUWE1 is essential for endoreplication of salivary gland cells and its knockdown results in the inability of these cells to replicate DNA. Remarkably, dHUWE1 is a survival factor that prevents premature activation of JNK signaling, thus preventing the disintegration of the salivary gland, which occurs physiologically during pupal stages. This function of dHUWE1 is general, as its inhibitory effect is observed also during eye development and at the organismal level. Epistatic studies revealed that the loss of dHUWE1 is compensated by dMyc proeitn expression or the loss of dmP53. dHUWE1 is therefore a conserved survival factor that regulates organ formation during Drosophila development. Full article
(This article belongs to the Special Issue Ubiquitination in Health and Disease)
Figures

Figure 1

Open AccessArticle The Effect of Neurotoxin MPTP and Neuroprotector Isatin on the Profile of Ubiquitinated Brain Mitochondrial Proteins
Received: 28 June 2018 / Revised: 26 July 2018 / Accepted: 27 July 2018 / Published: 31 July 2018
Cited by 2 | PDF Full-text (1661 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Mitochondria are a crucial target for the actions of neurotoxins, causing symptoms of Parkinson’s disease in various experimental animal models, and also neuroprotectors. There is evidence that mitochondrial dysfunction induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) influences functioning of the ubiquitin-proteasomal system (UPS) responsible
[...] Read more.
Mitochondria are a crucial target for the actions of neurotoxins, causing symptoms of Parkinson’s disease in various experimental animal models, and also neuroprotectors. There is evidence that mitochondrial dysfunction induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) influences functioning of the ubiquitin-proteasomal system (UPS) responsible for selective proteolytic degradation of proteins from various intracellular compartments (including mitochondria) and neuroprotective effects of certain anti-Parkisonian agents (monoamine oxidase inhibitors) may be associated with their effects on the UPS. In this study, we have investigated the effect of the neurotoxin MPTP and neuroprotector isatin, and their combination on the profile of ubiquitinated brain mitochondrial proteins. The development of movement disorders induced by MPTP administration caused dramatic changes in the profile of ubiquitinated proteins associated with mitochondria. Pretreatment with the neuroprotector isatin decreased manifestations of MPTP-induced Parkinsonism, and had a significant impact on the profile of ubiquitinated mitochondrial proteins (including oxidative modified proteins). Administration of isatin alone to intact mice also influenced the profile of ubiquitinated mitochondrial proteins, and increased the proportion of oxidized proteins carrying the ubiquitination signature. These alterations in the ubiquitination of mitochondrial proteins observed within 2 h after administration of MPTP and isatin obviously reflect immediate short-term biological responses to these treatments. Full article
(This article belongs to the Special Issue Ubiquitination in Health and Disease)
Figures

Figure 1

Review

Jump to: Research, Other

Open AccessReview Control of DNA Replication Initiation by Ubiquitin
Cells 2018, 7(10), 146; https://doi.org/10.3390/cells7100146
Received: 5 September 2018 / Revised: 18 September 2018 / Accepted: 19 September 2018 / Published: 20 September 2018
PDF Full-text (1308 KB) | HTML Full-text | XML Full-text
Abstract
Eukaryotic cells divide by accomplishing a program of events in which the replication of the genome is a fundamental part. To ensure all cells have an accurate copy of the genome, DNA replication occurs only once per cell cycle and is controlled by
[...] Read more.
Eukaryotic cells divide by accomplishing a program of events in which the replication of the genome is a fundamental part. To ensure all cells have an accurate copy of the genome, DNA replication occurs only once per cell cycle and is controlled by numerous pathways. A key step in this process is the initiation of DNA replication in which certain regions of DNA are marked as competent to replicate. Moreover, initiation of DNA replication needs to be coordinated with other cell cycle processes. At the molecular level, initiation of DNA replication relies, among other mechanisms, upon post-translational modifications, including the conjugation and hydrolysis of ubiquitin. An example is the precise control of the levels of the DNA replication initiation protein Cdt1 and its inhibitor Geminin by ubiquitin-mediated proteasomal degradation. This control ensures that DNA replication occurs with the right timing during the cell cycle, thereby avoiding re-replication events. Here, we review the events that involve ubiquitin signalling during DNA replication initiation, and how they are linked to human disease. Full article
(This article belongs to the Special Issue Ubiquitination in Health and Disease)
Figures

Figure 1

Open AccessReview Ubiquitin Regulation: The Histone Modifying Enzyme′s Story
Received: 26 July 2018 / Revised: 22 August 2018 / Accepted: 23 August 2018 / Published: 27 August 2018
PDF Full-text (1009 KB) | HTML Full-text | XML Full-text
Abstract
Histone post-translational modifications influence many fundamental cellular events by regulating chromatin structure and gene transcriptional activity. These modifications are highly dynamic and tightly controlled, with many enzymes devoted to the addition and removal of these modifications. Interestingly, these modifying enzymes are themselves fine-tuned
[...] Read more.
Histone post-translational modifications influence many fundamental cellular events by regulating chromatin structure and gene transcriptional activity. These modifications are highly dynamic and tightly controlled, with many enzymes devoted to the addition and removal of these modifications. Interestingly, these modifying enzymes are themselves fine-tuned and precisely regulated at the level of protein turnover by ubiquitin-proteasomal processing. Here, we focus on recent progress centered on the mechanisms regulating ubiquitination of histone modifying enzymes, including ubiquitin proteasomal degradation and the reverse process of deubiquitination. We will also discuss the potential pathophysiological significance of these processes. Full article
(This article belongs to the Special Issue Ubiquitination in Health and Disease)
Figures

Graphical abstract

Open AccessReview Deubiquitinating Enzymes Related to Autophagy: New Therapeutic Opportunities?
Received: 31 July 2018 / Revised: 13 August 2018 / Accepted: 17 August 2018 / Published: 19 August 2018
Cited by 1 | PDF Full-text (1757 KB) | HTML Full-text | XML Full-text
Abstract
Autophagy is an evolutionary conserved catabolic process that allows for the degradation of intracellular components by lysosomes. This process can be triggered by nutrient deprivation, microbial infections or other challenges to promote cell survival under these stressed conditions. However, basal levels of autophagy
[...] Read more.
Autophagy is an evolutionary conserved catabolic process that allows for the degradation of intracellular components by lysosomes. This process can be triggered by nutrient deprivation, microbial infections or other challenges to promote cell survival under these stressed conditions. However, basal levels of autophagy are also crucial for the maintenance of proper cellular homeostasis by ensuring the selective removal of protein aggregates and dysfunctional organelles. A tight regulation of this process is essential for cellular survival and organismal health. Indeed, deregulation of autophagy is associated with a broad range of pathologies such as neuronal degeneration, inflammatory diseases, and cancer progression. Ubiquitination and deubiquitination of autophagy substrates, as well as components of the autophagic machinery, are critical regulatory mechanisms of autophagy. Here, we review the main evidence implicating deubiquitinating enzymes (DUBs) in the regulation of autophagy. We also discuss how they may constitute new therapeutic opportunities in the treatment of pathologies such as cancers, neurodegenerative diseases or infections. Full article
(This article belongs to the Special Issue Ubiquitination in Health and Disease)
Figures

Figure 1

Open AccessFeature PaperReview Lafora Disease: A Ubiquitination-Related Pathology
Received: 3 July 2018 / Revised: 23 July 2018 / Accepted: 24 July 2018 / Published: 26 July 2018
PDF Full-text (1815 KB) | HTML Full-text | XML Full-text
Abstract
Lafora disease (LD, OMIM254780) is a rare and fatal form of progressive myoclonus epilepsy (PME). Among PMEs, LD is unique because of the rapid neurological deterioration of the patients and the appearance in brain and peripheral tissues of insoluble glycogen-like (polyglucosan) inclusions, named
[...] Read more.
Lafora disease (LD, OMIM254780) is a rare and fatal form of progressive myoclonus epilepsy (PME). Among PMEs, LD is unique because of the rapid neurological deterioration of the patients and the appearance in brain and peripheral tissues of insoluble glycogen-like (polyglucosan) inclusions, named Lafora bodies (LBs). LD is caused by mutations in the EPM2A gene, encoding the dual phosphatase laforin, or the EPM2B gene, encoding the E3-ubiquitin ligase malin. Laforin and malin form a functional complex that is involved in the regulation of glycogen synthesis. Thus, in the absence of a functional complex glycogen accumulates in LBs. In addition, it has been suggested that the laforin-malin complex participates in alternative physiological pathways, such as intracellular protein degradation, oxidative stress, and the endoplasmic reticulum unfolded protein response. In this work we review the possible cellular functions of laforin and malin with a special focus on their role in the ubiquitination of specific substrates. We also discuss here the pathological consequences of defects in laforin or malin functions, as well as the therapeutic strategies that are being explored for LD. Full article
(This article belongs to the Special Issue Ubiquitination in Health and Disease)
Figures

Figure 1

Other

Jump to: Research, Review

Open AccessErratum Erratum: Polge, C., et al. UBE2E1 Is Preferentially Expressed in the Cytoplasm of Slow-Twitch Fibers and Protects Skeletal Muscles from Exacerbated Atrophy upon Dexamethasone Treatment. Cells 2018, 7, 214
Cells 2018, 7(12), 242; https://doi.org/10.3390/cells7120242
Received: 29 November 2018 / Accepted: 30 November 2018 / Published: 4 December 2018
Cited by 1 | PDF Full-text (191 KB) | HTML Full-text | XML Full-text
Abstract
Change in author names (order). [...] Full article
(This article belongs to the Special Issue Ubiquitination in Health and Disease)
Cells EISSN 2073-4409 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top