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Neurochemistry International Jul 2017The process of protein modification by adding or detaching small ubiquitin-like modifiers (SUMO) proteins, called SUMOylation, contributes to the regulation of numerous... (Review)
Review
The process of protein modification by adding or detaching small ubiquitin-like modifiers (SUMO) proteins, called SUMOylation, contributes to the regulation of numerous processes in eukaryotic cells. SUMOylation also represents a key response and adaption mechanism to different forms of metabolic stress. The central nervous system (CNS) and neurons in particular are highly susceptible to hypoxic-ischemic stress due to the lack of significant oxygen and energy reserves. SUMOylation is observed in many molecular responses to metabolic stress in the brain, and is therefore supposed to represent an endogenous neuroprotective mechanism. However, the detailed roles of SUMOylation during CNS hypoxia-ischemia are not well understood so far. Moreover, SUMOylation is subjected to complex regulatory mechanisms and might exert protective, but also detrimental processes during hypoxic-ischemic stress. This review provides a comprehensive overview on SUMOylation processes under physiological and pathological conditions in the CNS. A particular spotlight is set on clinically relevant hypoxic-ischemic conditions such as stroke by focusing on peri- and postischemic SUMOylation in neurons and astrocytes. The review describes relevant SUMOylation targets in these cells to discuss confirmed and supposed downstream mechanisms potentially contributing to neuroprotection, but also to sometimes detrimental processes. The review further provides unique insights into the time course of SUMO responses during cerebral ischemia in different cerebral cell populations. This includes neurons, astrocytes, but also phagocytes that become activated (microglia) and/or migrate (macrophages/monocytes) to the ischemic CNS. Based on this compact knowledge, the review finally suggests potential directions for future basic and translational research.
Topics: Animals; Brain Ischemia; Humans; Hypoxia, Brain; Neuroprotection; Neuroprotective Agents; Sumoylation
PubMed: 28323006
DOI: 10.1016/j.neuint.2017.03.011 -
Biochimica Et Biophysica Acta. Reviews... Dec 2018Cells and soluble mediators of the innate and adaptive immune systems are fundamental components of the tumor microenvironment. Nuclear factors, e.g. transcription... (Review)
Review
Cells and soluble mediators of the innate and adaptive immune systems are fundamental components of the tumor microenvironment. Nuclear factors, e.g. transcription factors (TFs) and oncoproteins/cancer suppressors, play important roles in controlling cytokine functions leading to the development, maintenance and metastasis of cancers. Studies focusing on the regulators of the pro-tumorigenic microenvironment are particularly pertinent to early diagnosis and potential development of targeted cancer therapeutics. This review is motivated by new insights into the molecular dynamics of ubiquitination and SUMOylation, which post-translationally modify tumor suppressor TFs, leading to initiation and progression of various cancers like prostate, colorectal, liver and breast cancers. These modification pathways are differentially modulated under various stimuli or stresses in order to sustain the oncogenic potentials. We deliberate on the vicious cycle of infection and chronic inflammation-driven processes of ubiquitination and SUMOylation, resulting in the imbalance in cytokine profiles in the pro-tumorigenic microenvironment.
Topics: Animals; Humans; Inflammation; Neoplasms; Sumoylation; Tumor Microenvironment; Ubiquitination
PubMed: 30318471
DOI: 10.1016/j.bbcan.2018.08.002 -
International Journal of Molecular... Sep 2021Cardiovascular disease (CVD) is a common disease caused by many factors, including atherosclerosis, congenital heart disease, heart failure, and ischemic cardiomyopathy.... (Review)
Review
Cardiovascular disease (CVD) is a common disease caused by many factors, including atherosclerosis, congenital heart disease, heart failure, and ischemic cardiomyopathy. CVD has been regarded as one of the most common diseases and has a severe impact on the life quality of patients. The main features of CVD include high morbidity and mortality, which seriously threaten human health. SUMO proteins covalently conjugate lysine residues with a large number of substrate proteins, and SUMOylation regulates the function of target proteins and participates in cellular activities. Under certain pathological conditions, SUMOylation of proteins related to cardiovascular development and function are greatly changed. Numerous studies have suggested that SUMOylation of substrates plays critical roles in normal cardiovascular development and function. We reviewed the research progress of SUMOylation in cardiovascular development and function, and the regulation of protein SUMOylation may be applied as a potential therapeutic strategy for CVD treatment.
Topics: Animals; Cardiovascular Diseases; Cysteine Endopeptidases; Heart; Humans; Lysine; Molecular Targeted Therapy; Organogenesis; Signal Transduction; Small Ubiquitin-Related Modifier Proteins; Sumoylation; Ubiquitin-Conjugating Enzymes
PubMed: 34638970
DOI: 10.3390/ijms221910618 -
The Journal of Biological Chemistry Oct 2019Ubiquitin and the ∼20 human ubiquitin-like proteins regulate numerous aspects of cell biology via interlinked mechanisms that have not been fully elucidated. Sha now...
Ubiquitin and the ∼20 human ubiquitin-like proteins regulate numerous aspects of cell biology via interlinked mechanisms that have not been fully elucidated. Sha now explore the interplay between ubiquitylation and SUMOylation, finding that inhibition of ubiquitylation enhances SUMOylation of hundreds of newly synthesized proteins and that the resultant pools are stored in phase-separated protein condensates called PML nuclear bodies. These unexpected outcomes identify a new role for SUMOylation and raise new questions about cell behavior under normal and stress conditions.
Topics: Humans; Intranuclear Inclusion Bodies; Nuclear Proteins; Sumoylation; Ubiquitin; Ubiquitination
PubMed: 31628197
DOI: 10.1074/jbc.H119.011037 -
RNA Biology 2018Spliceosomal proteins have been revealed as SUMO conjugation targets. Moreover, we have reported that many of these are in a SUMO-conjugated form when bound to a... (Review)
Review
Spliceosomal proteins have been revealed as SUMO conjugation targets. Moreover, we have reported that many of these are in a SUMO-conjugated form when bound to a pre-mRNA substrate during a splicing reaction. We demonstrated that SUMOylation of Prp3 (PRPF3), a component of the U4/U6 di-snRNP, is required for U4/U6•U5 tri-snRNP formation and/or recruitment to active spliceosomes. Expanding upon our previous results, we have shown that the splicing factor SRSF1 stimulates SUMO conjugation to several spliceosomal proteins. Given the relevance of the splicing process, as well as the complex and dynamic nature of its governing machinery, the spliceosome, the molecular mechanisms that modulate its function represent an attractive topic of research. We posit that SUMO conjugation could represent a way of modulating spliceosome assembly and thus, splicing efficiency. How cycles of SUMOylation/de-SUMOylation of spliceosomal proteins become integrated throughout the highly choreographed spliceosomal cycle awaits further investigation.
Topics: Animals; Humans; Nuclear Proteins; RNA Splicing; RNA Splicing Factors; Ribonucleoprotein, U4-U6 Small Nuclear; SUMO-1 Protein; Sumoylation
PubMed: 29741121
DOI: 10.1080/15476286.2018.1457936 -
Trends in Biochemical Sciences May 2023Protein SUMOylation is one of the most prevalent post-translational modifications (PTMs) and important for maintaining cellular homeostasis in response to various...
Protein SUMOylation is one of the most prevalent post-translational modifications (PTMs) and important for maintaining cellular homeostasis in response to various cellular stresses. Emerging evidence reveals the role of liquid-liquid phase separation (LLPS)/biomolecular condensates in cellular SUMOylation, potentially solving a puzzle regarding the cellular mechanism of SUMOylation regulation.
Topics: Sumoylation; Protein Processing, Post-Translational
PubMed: 36621339
DOI: 10.1016/j.tibs.2022.12.003 -
Journal of Neurovirology Aug 2021The conjugation of small ubiquitin-like modifier (SUMO) proteins to substrates is a well-described post-translational modification that regulates protein activity,... (Review)
Review
The conjugation of small ubiquitin-like modifier (SUMO) proteins to substrates is a well-described post-translational modification that regulates protein activity, subcellular localization, and protein-protein interactions for a variety of downstream cellular activities. Several studies describe SUMOylation as an essential post-translational modification for successful viral infection across a broad range of viruses, including RNA and DNA viruses, both enveloped and un-enveloped. These viruses include but are not limited to herpes viruses, human immunodeficiency virus-1, and coronaviruses. In addition to the SUMOylation of viral proteins during infection, evidence shows that viruses manipulate the SUMO pathway for host protein SUMOylation. SUMOylation of host and viral proteins greatly impacts host innate immunity through viral manipulation of the host SUMOylation machinery to promote viral replication and pathogenesis. Other post-translational modifications like phosphorylation can also modulate SUMO function. For example, phosphorylation of COUP-TF interacting protein 2 (CTIP2) leads to its SUMOylation and subsequent proteasomal degradation. The SUMOylation of CTIP2 and subsequent degradation prevents CTIP2-mediated recruitment of a multi-enzymatic complex to the HIV-1 promoter that usually prevents the transcription of integrated viral DNA. Thus, the "SUMO switch" could have implications for CTIP2-mediated transcriptional repression of HIV-1 in latency and viral persistence. In this review, we describe the consequences of SUMO in innate immunity and then focus on the various ways that viral pathogens have evolved to hijack the conserved SUMO machinery. Increased understanding of the many roles of SUMOylation in viral infections can lead to novel insight into the regulation of viral pathogenesis with the potential to uncover new targets for antiviral therapies.
Topics: Animals; Host-Pathogen Interactions; Humans; Immunity, Innate; Protein Processing, Post-Translational; SUMO-1 Protein; Sumoylation; Virus Diseases
PubMed: 34342851
DOI: 10.1007/s13365-021-00995-9 -
Chromosoma Mar 2015Increasing evidence indicates that besides promoters, enhancers, and epigenetic modifications, nuclear organization is another parameter contributing to optimal control... (Review)
Review
Increasing evidence indicates that besides promoters, enhancers, and epigenetic modifications, nuclear organization is another parameter contributing to optimal control of gene expression. Although differences between species exist, the influence of gene positioning on expression seems to be a conserved feature from yeast to Drosophila and mammals. The nuclear periphery is one of the nuclear compartments implicated in gene regulation. It consists of the nuclear envelope (NE) and the nuclear pore complexes (NPC), which have distinct roles in the control of gene expression. The NPC has recently been shown to tether proteins involved in the sumoylation pathway. Here, we will focus on the importance of gene positioning and NPC-linked sumoylation/desumoylation in transcription regulation. We will mainly discuss observations made in the yeast Saccharomyces cerevisiae model system and highlight potential parallels in metazoan species.
Topics: Animals; Gene Expression Regulation; Gene Order; Nuclear Pore; Saccharomyces cerevisiae; Sumoylation; Transcription, Genetic
PubMed: 25171917
DOI: 10.1007/s00412-014-0481-x -
The FEBS Journal Oct 2015SUMOylation is a post-translational modification that regulates a multitude of cellular processes, including replication, cell-cycle progression, protein transport and... (Review)
Review
SUMOylation is a post-translational modification that regulates a multitude of cellular processes, including replication, cell-cycle progression, protein transport and the DNA damage response. Similar to ubiquitin, SUMO (small ubiquitin-like modifier) is covalently attached to target proteins in a reversible process via an enzymatic cascade. SUMOylation is essential for nearly all eukaryotic organisms, and deregulation of the SUMO system is associated with human diseases such as cancer and neurodegenerative diseases. Therefore, it is of great interest to understand the regulation and dynamics of this post-translational modification. Within the last decade, mass spectrometry analyses of SUMO proteomes have overcome several obstacles, greatly expanding the number of known SUMO target proteins. In this review, we briefly outline the basic concepts of the SUMO system, and discuss the potential of proteomic approaches to decipher SUMOylation patterns in order to understand the role of SUMO in health and disease.
Topics: Humans; Ligases; Peptide Hydrolases; Protein Processing, Post-Translational; Proteins; Proteomics; Small Ubiquitin-Related Modifier Proteins; Sumoylation
PubMed: 26185901
DOI: 10.1111/febs.13378 -
Current Issues in Molecular Biology 2021DNA replication is a tightly regulated conserved process that ensures the faithful transmission of genetic material to define heritable phenotypic traits. Perturbations... (Review)
Review
DNA replication is a tightly regulated conserved process that ensures the faithful transmission of genetic material to define heritable phenotypic traits. Perturbations in this process result in genomic instability, mutagenesis, and diseases, including malignancy. Proteins involved in the initiation, progression, and termination of DNA replication are subject to a plethora of reversible post-translational modifications (PTMs) to provide a proper temporal and spatial control of replication. Among these, modifications involving the covalent attachment of the small protein ubiquitin or the small ubiquitin-like modifier (SUMO) to replication and replication-associated proteins are particularly important for the proper regulation of DNA replication as well as for optimal cellular responses to replication stress. In this article, we describe how the ubiquitination and SUMOylation processes impact DNA replication in eukaryotes and highlight the consequences of deregulated signals emanating from these two versatile regulatory pathways on cellular activities.
Topics: Animals; Cell Cycle; Cell Proliferation; DNA Damage; DNA Replication; Humans; Proteasome Endopeptidase Complex; Small Ubiquitin-Related Modifier Proteins; Sumoylation; Ubiquitin
PubMed: 32606249
DOI: 10.21775/cimb.040.189