Current Issues in Molecular Biology

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Open AccessReview

Ubiquitination and SUMOylation of Amyloid and Amyloid-Like Proteins in Health and Disease

by Lenzie Ford, Luana Fioriti and Eric R. Kandel

Curr. Issues Mol. Biol. 2020, 35(1), 195-230; https://doi.org/10.21775/cimb.035.195 - 18 Aug 2019

Cited by 5 | Viewed by 610

Post-translational modifications (PTMs) play important roles in altering the structure and function of proteins. In this article, we focus on ubiquitination and SUMOylation of amyloidogenic proteins. We discuss the functional contributions of PTMs on proteins involved in amyloid-related diseases as well as the [...] Read more.

Post-translational modifications (PTMs) play important roles in altering the structure and function of proteins. In this article, we focus on ubiquitination and SUMOylation of amyloidogenic proteins. We discuss the functional contributions of PTMs on proteins involved in amyloid-related diseases as well as the aberrant PTM signatures of the disease agents. In addition, we extend our discussion to the nascent field of functional amyloids, a subclass of amyloids that perform physiological functions. Here, we present examples from mammals and yeast to gain insight into physiological regulation of amyloid-like proteins. Full article

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Open AccessReview

Ubiquitination and SUMOylation in HIV Infection: Friends and Foes

by Marta Colomer-Lluch, Sergio Castro-Gonzalez and Ruth Serra-Moreno

Curr. Issues Mol. Biol. 2020, 35(1), 159-194; https://doi.org/10.21775/cimb.035.159 - 18 Aug 2019

Cited by 10 | Viewed by 524

Abstract

As intracellular parasites, viruses hijack the cellular machinery to facilitate their replication and spread. This includes favouring the expression of their viral genes over host genes, appropriation of cellular molecules, and manipulation of signalling pathways, including the post-translational machinery. HIV, the causative agent [...] Read more.

As intracellular parasites, viruses hijack the cellular machinery to facilitate their replication and spread. This includes favouring the expression of their viral genes over host genes, appropriation of cellular molecules, and manipulation of signalling pathways, including the post-translational machinery. HIV, the causative agent of AIDS, is notorious for using post-translational modifications to generate infectious particles. Here, we discuss the mechanisms by which HIV usurps the ubiquitin and SUMO pathways to modify both viral and host factors to achieve a productive infection, and also how the host innate sensing system uses these post-translational modifications to hinder HIV replication. Full article

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Open AccessReview

Ubiquitin and SUMO Modifications in Caenorhabditis elegans Stress Response

by Krzysztof Drabikowski

Curr. Issues Mol. Biol. 2020, 35(1), 145-158; https://doi.org/10.21775/cimb.035.145 - 18 Aug 2019

Cited by 5 | Viewed by 558

Abstract

Post-translational protein modifications by ubiquitin, SUMO and other ubiquitin-like modifiers is common and essential for all eukaryotic organisms. Ubiquitin, SUMO and other ubiquitin-like modifiers are attached to target proteins by a set of related but distinct enzymes including activating enzyme, conjugating enzyme, a [...] Read more.

Post-translational protein modifications by ubiquitin, SUMO and other ubiquitin-like modifiers is common and essential for all eukaryotic organisms. Ubiquitin, SUMO and other ubiquitin-like modifiers are attached to target proteins by a set of related but distinct enzymes including activating enzyme, conjugating enzyme, a ligase and in some cases auxiliary proteins. Both ubiquitin and SUMO proteins regulate most physiological processes in cells and often interdependence of the protein modifications can be observed. Discoveries of ubiquitin and SUMO function have been predominantly driven by studies in cell systems and by in vitro approaches. Investigations of post-translational modifications in Caenorhabditis elegans promises new avenues in ubiquitin and SUMO research. It enables a whole organism approach to study post-translational modifications in development, stress, ageing and in disease models. The biochemical mechanisms of ubiquitin and SUMO modifications are essentially conserved in C. elegans and have been described elsewhere. Thus, this review focuses on emerging research areas where research in C. elegans is advantageous and strongly advances the field of post-translational modifications by ubiquitin and SUMO. Full article

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Open AccessReview

The Role of SUMOylation and Ubiquitination in Brain Ischaemia: Critical Concepts and Clinical Implications

by Joshua D. Bernstock, Daniel G. Ye, Dagoberto Estevez, Gustavo Chagoya, Ya-Chao Wang, Florian Gessler, John M. Hallenbeck and Wei Yang

Curr. Issues Mol. Biol. 2020, 35(1), 127-144; https://doi.org/10.21775/cimb.035.127 - 18 Aug 2019

Cited by 5 | Viewed by 627

Abstract

Brain ischaemia is a severe form of metabolic stress that activates a cascade of pathological events involving many signalling pathways. Modulation of these pathways is largely mediated by post-translational modifications (PTMs). Indeed, PTMs can rapidly modify pre-existing proteins by attaching chemical or polypeptide [...] Read more.

Brain ischaemia is a severe form of metabolic stress that activates a cascade of pathological events involving many signalling pathways. Modulation of these pathways is largely mediated by post-translational modifications (PTMs). Indeed, PTMs can rapidly modify pre-existing proteins by attaching chemical or polypeptide moieties to selected amino acid residues, altering their functions, stability, subcellular localizations, or interactions with other proteins. Subsequently, related signalling pathways can be substantially affected. Thus, PTMs are widely deployed by cells as an adaptive strategy at the front line to efficiently cope with internal and external stresses. Many types of PTMs have been identified, including phosphorylation, O-GlcNAcylation, small ubiquitin-like modifier (SUMO) modification (SUMOylation), and ubiquitination. All these PTMs have been studied in brain ischaemia to some extent. In particular, a large body of evidence has demonstrated that both global SUMOylation and ubiquitination are massively activated after brain ischaemia, and this activation may play a critical role in defining the fate and function of cells in the post-ischaemic brain. The goal of this review will be to summarize the current findings on SUMOylation and ubiquitination in brain ischaemia and discuss their clinical implications. Full article

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Open AccessReview

Roles of Ubiquitination and SUMOylation in the Regulation of Angiogenesis

by Andrea Rabellino, Cristina Andreani and Pier Paolo Scaglioni

Curr. Issues Mol. Biol. 2020, 35(1), 109-126; https://doi.org/10.21775/cimb.035.109 - 18 Aug 2019

Cited by 9 | Viewed by 660

Abstract

The generation of new blood vessels from the existing vasculature is a dynamic and complex mechanism known as angiogenesis. Angiogenesis occurs during the entire lifespan of vertebrates and participates in many physiological processes. Furthermore, angiogenesis is also actively involved in many human diseases [...] Read more.

The generation of new blood vessels from the existing vasculature is a dynamic and complex mechanism known as angiogenesis. Angiogenesis occurs during the entire lifespan of vertebrates and participates in many physiological processes. Furthermore, angiogenesis is also actively involved in many human diseases and disorders, including cancer, obesity and infections. Several inter-connected molecular pathways regulate angiogenesis, and post-translational modifications, such as phosphorylation, ubiquitination and SUMOylation, tightly regulate these mechanisms and play a key role in the control of the process. Here, we describe in detail the roles of ubiquitination and SUMOylation in the regulation of angiogenesis. Full article

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Open AccessReview

Role of Ubiquitin and SUMO in Intracellular Trafficking

by Maria Sundvall

Curr. Issues Mol. Biol. 2020, 35(1), 99-108; https://doi.org/10.21775/cimb.035.099 - 18 Aug 2019

Cited by 8 | Viewed by 527

Abstract

Precise location of proteins at a given time within a cell is essential to convey specific signals and result in a relevant functional outcome. Small ubiquitin-like modifications, such as ubiquitin and SUMO, represent a delicate and diverse way to transiently regulate intracellular trafficking [...] Read more.

Precise location of proteins at a given time within a cell is essential to convey specific signals and result in a relevant functional outcome. Small ubiquitin-like modifications, such as ubiquitin and SUMO, represent a delicate and diverse way to transiently regulate intracellular trafficking events of existing proteins in cells. Trafficking of multiple proteins is controlled reversibly by ubiquitin and/or SUMO directly or indirectly via regulation of transport machinery components. Regulation is dynamic and multilayered, involving active crosstalk and interdependence between post-translational modifications. However, in most cases regulation appears very complex, and the mechanistic details regarding how ubiquitin and SUMO control protein location in cells are not yet fully understood. Moreover, most of the findings still lack in vivo evidence in multicellular organisms. Full article

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Open AccessReview

The Role of Ubiquitination and SUMOylation in Telomere Biology

by Michal Zalzman, W. Alex Meltzer, Benjamin A. Portney, Robert A. Brown and Aditi Gupta

Curr. Issues Mol. Biol. 2020, 35(1), 85-98; https://doi.org/10.21775/cimb.035.085 - 18 Aug 2019

Cited by 7 | Viewed by 659

Abstract

Telomeres are a unique structure of DNA repeats covered by proteins at the ends of the chromosomes that protect the coding regions of the genome and function as a biological clock. They require a tight regulation of the factors covering and protecting their [...] Read more.

Telomeres are a unique structure of DNA repeats covered by proteins at the ends of the chromosomes that protect the coding regions of the genome and function as a biological clock. They require a tight regulation of the factors covering and protecting their structure, as they are shortened with each cell division to limit the ability of cells to replicate uncontrollably. Additionally, they protect the chromosome ends from DNA damage responses and thereby, prevent genomic instability. Telomere dysfunction can lead to chromosomal abnormalities and cancer. Therefore, dysregulation of any of the factors that regulate the integrity of the telomeres will have implications to chromosomal stability, replicative lifespan and may lead to cell transformation. This review will cover the main factors participating in the normal function of the telomeres and how these are regulated by the ubiquitin and SUMO systems. Accumulating evidence indicate that the ubiquitin and SUMO pathways are significant regulators of the shelterin complex and other chromatin modifiers, which are important for telomere structure integrity. Furthermore, the crosstalk between these two pathways has been reported in telomeric DNA repair. A better understanding of the factors contributing to telomere biology, and how they are regulated, is important for the design of new strategies for cancer therapies and regenerative medicine. Full article

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Open AccessReview

Roles of Ubiquitination and SUMOylation in DNA Damage Response

by Siyuan Su, Yanqiong Zhang and Pengda Liu

Curr. Issues Mol. Biol. 2020, 35(1), 59-84; https://doi.org/10.21775/cimb.035.059 - 18 Aug 2019

Cited by 21 | Viewed by 1156

Abstract

Ubiquitin and ubiquitin-like modifiers, such as SUMO, exert distinct physiological functions by conjugating to protein substrates. Ubiquitination or SUMOylation of protein substrates determine the fate of modified proteins, including proteasomal degradation, cellular re-localization, alternations in binding partners and serving as a protein-binding platform, [...] Read more.

Ubiquitin and ubiquitin-like modifiers, such as SUMO, exert distinct physiological functions by conjugating to protein substrates. Ubiquitination or SUMOylation of protein substrates determine the fate of modified proteins, including proteasomal degradation, cellular re-localization, alternations in binding partners and serving as a protein-binding platform, in a ubiquitin or SUMO linkage-dependent manner. DNA damage occurs constantly in living organisms but is also repaired by distinct tightly controlled mechanisms including homologous recombination, non-homologous end joining, inter-strand crosslink repair, nucleotide excision repair and base excision repair. On sensing damaged DNA, a ubiquitination/SUMOylation landscape is established to recruit DNA damage repair factors. Meanwhile, misloaded and mission-completed repair factors will be turned over by ubiquitin or SUMO modifications as well. These ubiquitination and SUMOylation events are tightly controlled by both E3 ubiquitin/SUMO ligases and deubiquitinases/deSUMOylases. In this review, we will summarize identified ubiquitin and SUMO-related modifications and their function in distinct DNA damage repair pathways, and provide evidence for responsible E3 ligases, deubiquitinases, SUMOylases and deSUMOylases in these processes. Given that genome instability leads to human disorders including cancer, understanding detailed molecular mechanisms for ubiquitin and SUMO-related regulations in DNA damage response may provide novel insights into therapeutic modalities to treat human diseases associated with deregulated DNA damage response. Full article

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Open AccessReview

Interplay between the Ubiquitin Proteasome System and Mitochondria for Protein Homeostasis

by Mafalda Escobar-Henriques, Selver Altin and Fabian den Brave

Curr. Issues Mol. Biol. 2020, 35(1), 35-58; https://doi.org/10.21775/cimb.035.035 - 18 Aug 2019

Cited by 13 | Viewed by 720

Abstract

Eukaryotic cells are subdivided into membrane-bound compartments specialized in different cellular functions and requiring dedicated sets of proteins. Although cells developed compartment-specific mechanisms for protein quality control, chaperones and ubiquitin are generally required for maintaining cellular proteostasis. Proteotoxic stress is signalled from one [...] Read more.

Eukaryotic cells are subdivided into membrane-bound compartments specialized in different cellular functions and requiring dedicated sets of proteins. Although cells developed compartment-specific mechanisms for protein quality control, chaperones and ubiquitin are generally required for maintaining cellular proteostasis. Proteotoxic stress is signalled from one compartment into another to adjust the cellular stress response. Moreover, transport of misfolded proteins between different compartments can buffer local defects in protein quality control. Mitochondria are special organelles in that they possess an own expression, folding and proteolytic machinery, of bacterial origin, which do not have ubiquitin. Nevertheless, the importance of extensive cross-talk between mitochondria and other subcellular compartments is increasingly clear. Here, we will present local quality control mechanisms and discuss how cellular proteostasis is affected by the interplay between mitochondria and the ubiquitin proteasome system. Full article

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Open AccessReview

Progress in the Discovery of Small Molecule Modulators of DeSUMOylation

by Shiyao Chen, Duoling Dong, Weixiang Xin and Huchen Zhou

Curr. Issues Mol. Biol. 2020, 35(1), 17-34; https://doi.org/10.21775/cimb.035.017 - 18 Aug 2019

Cited by 10 | Viewed by 635

Abstract

SUMOylation and DeSUMOylation are reversible protein post-translational modification (PTM) processes involving small ubiquitin-like modifier (SUMO) proteins. These processes have indispensable roles in various cellular processes, such as subcellular localization, gene transcription, and DNA replication and repair. Over the past decade, increasing attention has [...] Read more.

SUMOylation and DeSUMOylation are reversible protein post-translational modification (PTM) processes involving small ubiquitin-like modifier (SUMO) proteins. These processes have indispensable roles in various cellular processes, such as subcellular localization, gene transcription, and DNA replication and repair. Over the past decade, increasing attention has been given to SUMO-related pathways as potential therapeutic targets. The Sentrin/SUMO-specific protease (SENP), which is responsible for deSUMOylation, has been proposed as a potential therapeutic target in the treatment of cancers and cardiac disorders. Unfortunately, no SENP inhibitor has yet reached clinical trials. In this review, we focus on advances in the development of SENP inhibitors in the past decade. Full article

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Open AccessReview

Recent Highlights: Onco Viral Exploitation of the SUMO System

by Domenico Mattoscio, Alessandro Medda and Susanna Chiocca

Curr. Issues Mol. Biol. 2020, 35(1), 1-16; https://doi.org/10.21775/cimb.035.001 - 18 Aug 2019

Cited by 11 | Viewed by 458

Abstract

Small ubiquitin-like modifier (SUMO)ylation is a crucial post-translational modification that controls functions of a wide collection of proteins and biological processes. Hence, given its pleiotropic role, viruses have developed many approaches to usurp SUMO conjugation to exploit the cellular host environment for their [...] Read more.

Small ubiquitin-like modifier (SUMO)ylation is a crucial post-translational modification that controls functions of a wide collection of proteins and biological processes. Hence, given its pleiotropic role, viruses have developed many approaches to usurp SUMO conjugation to exploit the cellular host environment for their own benefit. Consistently, cancer cells also frequently impact on SUMO to force cellular transformation, underlining the importance of SUMO in health and diseases. Therefore, after a brief introduction to the multistep SUMOylation pathway, in this review we will focus our attention on several examples of strategies adopted by oncogenic viruses to hijack SUMOylation in order to promote infection, persistence and malignant transformation of host cells. Full article

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Curr. Issues Mol. Biol., Volume 35, Issue 1 (January 2020) – 11 articles

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