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Cells Oct 2022Neurodegenerative diseases (NDDs) are irreversible, progressive diseases with no effective treatment. The hallmark of NDDs is the aggregation of misfolded, modified... (Review)
Review
Neurodegenerative diseases (NDDs) are irreversible, progressive diseases with no effective treatment. The hallmark of NDDs is the aggregation of misfolded, modified proteins, which impair neuronal vulnerability and cause brain damage. The loss of synaptic connection and the progressive loss of neurons result in cognitive defects. Several dysregulated proteins and overlapping molecular mechanisms contribute to the pathophysiology of NDDs. Post-translational modifications (PTMs) are essential regulators of protein function, trafficking, and maintaining neuronal hemostasis. The conjugation of a small ubiquitin-like modifier (SUMO) is a reversible, dynamic PTM required for synaptic and cognitive function. The onset and progression of neurodegenerative diseases are associated with aberrant SUMOylation. In this review, we have summarized the role of SUMOylation in regulating critical proteins involved in the onset and progression of several NDDs.
Topics: Humans; Sumoylation; Neurodegenerative Diseases; Small Ubiquitin-Related Modifier Proteins; Protein Processing, Post-Translational; Neurons
PubMed: 36359791
DOI: 10.3390/cells11213395 -
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 -
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 -
Current Issues in Molecular Biology 2016SUMOylation, much of a similar process like ubiquitination catches attention across various research groups as a potential therapeutic target to fight various infectious... (Review)
Review
SUMOylation, much of a similar process like ubiquitination catches attention across various research groups as a potential therapeutic target to fight various infectious and cancerous diseases. This idea take its strength from recent reports which unearth the molecular mechanisms of SUMOylation and its involvement in important diseases distributed across various kingdoms. At the beginning SUMOylation was considered a process affected only by viral diseases but subsequent reports enlighten its role in diseases caused by bacteria as well. This enhances the SUMOylation canvas and demanded more in-depth study of the process. The present review is an attempt to study the regulatory mechanism of genes when the natural SUMOylation pathway is disturbed, the cross-talk among SUMOylation and other post translational modifications, the role of miRNAs in controlling the function of transcripts, loading of RNA species into exosomes and the possible SUMOylation related therapeutic targets.
Topics: Animals; Antineoplastic Agents; Humans; Immunity, Innate; Inflammation; Molecular Targeted Therapy; Neoplasms; Small Ubiquitin-Related Modifier Proteins; Sumoylation
PubMed: 26234807
DOI: No ID Found -
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 -
Journal of Neurochemistry Jan 2021SUMOylation is a post-translational modification that regulates protein signalling and complex formation by adjusting the conformation or protein-protein interactions of... (Review)
Review
SUMOylation is a post-translational modification that regulates protein signalling and complex formation by adjusting the conformation or protein-protein interactions of the substrate protein. There is a compelling and rapidly expanding body of evidence that, in addition to SUMOylation of nuclear proteins, SUMOylation of extranuclear proteins contributes to the control of neuronal development, neuronal stress responses and synaptic transmission and plasticity. In this brief review we provide an update of recent developments in the identification of synaptic and synapse-associated SUMO target proteins and discuss the cell biological and functional implications of these discoveries.
Topics: Animals; Humans; Sumoylation; Synapses
PubMed: 32538470
DOI: 10.1111/jnc.15103 -
International Journal of Molecular... Mar 2022Post-translational modifications of proteins ensure optimized cellular processes, including proteostasis, regulated signaling, cell survival, and stress adaptation to... (Review)
Review
Post-translational modifications of proteins ensure optimized cellular processes, including proteostasis, regulated signaling, cell survival, and stress adaptation to maintain a balanced homeostatic state. Abnormal post-translational modifications are associated with cellular dysfunction and the occurrence of life-threatening diseases, such as cancer and neurodegenerative diseases. Therefore, some of the frequently seen protein modifications have been used as disease markers, while others are targeted for developing specific therapies. The ubiquitin and ubiquitin-like post-translational modifiers, namely, small ubiquitin-like modifier (SUMO) and neuronal precursor cell-expressed developmentally down-regulated protein 8 (NEDD8), share several features, such as protein structures, enzymatic cascades mediating the conjugation process, and targeted amino acid residues. Alterations in the regulatory mechanisms lead to aberrations in biological processes during tumorigenesis, including the regulation of tumor metabolism, immunological modulation of the tumor microenvironment, and cancer stem cell stemness, besides many more. Novel insights into ubiquitin and ubiquitin-like pathways involved in cancer biology reveal a potential interplay between ubiquitination, SUMOylation, and NEDDylation. This review outlines the current understandings of the regulatory mechanisms and assay capabilities of ubiquitination, SUMOylation, and NEDDylation. It will further highlight the role of ubiquitination, SUMOylation, and NEDDylation in tumorigenesis.
Topics: Carcinogenesis; Humans; Neoplasms; Protein Processing, Post-Translational; Proteins; Sumoylation; Tumor Microenvironment; Ubiquitin; Ubiquitination
PubMed: 35408841
DOI: 10.3390/ijms23073480 -
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 -
Molecules and Cells Oct 2011The traditional focus on the central dogma of molecular biology, from gene through RNA to protein, has now been replaced by the recognition of an additional mechanism.... (Review)
Review
The traditional focus on the central dogma of molecular biology, from gene through RNA to protein, has now been replaced by the recognition of an additional mechanism. The new regulatory mechanism, post-translational modifications to proteins, can actively alter protein function or activity introducing additional levels of functional complexity by altering cellular and sub-cellular location, protein interactions and the outcome of biochemical reaction chains. Modifications by ubiquitin (Ub) and ubiquitin-like modifiers systems are conserved in all eukaryotic organisms. One of them, small ubiquitin-like modifier (SUMO) is present in plants. The SUMO mechanism includes several isoforms of proteins that are involved in reactions of sumoylation and de-sumoylation. Sumoylation affects several important processes in plants. Outstanding among those are responses to environmental stresses. These may be abiotic stresses, such as phosphate deficiency, heat, low temperature, and drought, or biotic stressses, as well including defense reactions to pathogen infection. Also, the regulations of flowering time, cell growth and development, and nitrogen assimilation have recently been added to this list. Identification of SUMO targets is material to characterize the function of sumoylation or desumoylation. Affinity purification and mass spectrometric identification have been done lately in plants. Further SUMO noncovalent binding appears to have function in other model organisms and SUMO interacting proteins in plants will be of interest to plant biologists who dissect the dynamic function of SUMO. This review will discuss results of recent insights into the role of sumoylation in plants.
Topics: Animals; Environmental Exposure; Humans; Plant Physiological Phenomena; Plants; Protein Processing, Post-Translational; Small Ubiquitin-Related Modifier Proteins; Stress, Physiological; Sumoylation; Ubiquitin
PubMed: 21912873
DOI: 10.1007/s10059-011-0122-7 -
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