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Cell Communication and Signaling : CCS Jul 2017Viruses exploit various cellular processes for their own benefit, including counteracting anti-viral responses and regulating viral replication and propagation. In the... (Review)
Review
Viruses exploit various cellular processes for their own benefit, including counteracting anti-viral responses and regulating viral replication and propagation. In the past 20 years, protein sumoylation has emerged as an important post-translational modification that is manipulated by viruses to modulate anti-viral responses, viral replication, and viral pathogenesis. The process of sumoylation is a multi-step cascade where a small ubiquitin-like modifier (SUMO) is covalently attached to a conserved ΨKxD/E motif within a target protein, altering the function of the modified protein. Here we review how viruses manipulate the cellular machinery at each step of the sumoylation process to favor viral survival and pathogenesis.
Topics: Animals; Humans; Small Ubiquitin-Related Modifier Proteins; Sumoylation; Ubiquitin-Protein Ligase Complexes; Virus Diseases
PubMed: 28705221
DOI: 10.1186/s12964-017-0183-0 -
Cancer Science Feb 2022Small ubiquitin-like modifier (SUMO)ylation is one of the posttranslational modifications and is implicated in many tumor types. Modulation of SUMOylation can affect...
Small ubiquitin-like modifier (SUMO)ylation is one of the posttranslational modifications and is implicated in many tumor types. Modulation of SUMOylation can affect tumor progression, but the underlying mechanisms remain unclear. Here, we show that, for the first time, in uveal melanoma (UM), the most common intraocular malignancy in adults, global SUMOylation is upregulated and participates in tumor growth. Inhibition of SUMOylation in UM is sufficient to reduce tumor growth both in vitro and in vivo. Furthermore, we found that retinoblastoma protein (Rb) is a target protein and a critical downstream effector of the upregulated SUMOylation activity in UM. Increased SUMOylation of the Rb protein leads to its hyperphosphorylation and inactivation in UM cells, promoting UM cell proliferation. In summary, our results provide novel insight into the mechanism underlying SUMOylation-regulated tumor growth in UM.
Topics: Animals; Apoptosis; Cell Line, Tumor; Cell Proliferation; Humans; Melanoma; Mice; Phosphorylation; Retinoblastoma Binding Proteins; SUMO-1 Protein; Sumoylation; Ubiquitin-Protein Ligases; Uveal Neoplasms
PubMed: 34839558
DOI: 10.1111/cas.15223 -
Biomolecular Concepts Mar 2017The regulation of protein fate by modification with the small ubiquitin-related modifier (SUMO) plays an essential and crucial role in most cellular pathways.... (Review)
Review
The regulation of protein fate by modification with the small ubiquitin-related modifier (SUMO) plays an essential and crucial role in most cellular pathways. Sumoylation is highly dynamic due to the opposing activities of SUMO conjugation and SUMO deconjugation. SUMO conjugation is performed by the hierarchical action of E1, E2 and E3 enzymes, while its deconjugation involves SUMO-specific proteases. In this review, we summarize and compare the mechanistic principles of how SUMO gets conjugated to its substrate. We focus on the interplay of the E1, E2 and E3 enzymes and discuss how specificity could be achieved given the limited number of conjugating enzymes and the thousands of substrates.
Topics: SUMO-1 Protein; Substrate Specificity; Sumoylation; Ubiquitin; Ubiquitin-Protein Ligases
PubMed: 28284030
DOI: 10.1515/bmc-2016-0030 -
BMB Reports Feb 2019The small ubiquitin-related modification molecule (SUMO), one of the post-translational modification molecules, is involved in a variety of cellular functions where it... (Review)
Review
The small ubiquitin-related modification molecule (SUMO), one of the post-translational modification molecules, is involved in a variety of cellular functions where it regulates protein activity and stability, transcription, and cell cycling. Modulation of protein SUMOylation or deSUMOylation modification has been associated with regulation of carcinogenesis in breast cancer. In the dynamic processes of SUMOylation and deSUMOylation in a variety of cancers, SUMO proteases (SENPs), reverse SUMOylation by isopeptidase activity and SENPs are mostly elevated, and are related to poor patient prognosis. Although underlying mechanisms have been suggested for how SENPs participate in breast cancer tumorigenesis, such as through regulation of target protein transactivation, cancer cell survival, cell cycle, or other post-translational modification-related machinery recruitment, the effect of SENP isoform-specific inhibitors on the progression of breast cancer have not been well evaluated. This review will introduce the functions of SENP1 and SENP2 and the underlying signaling pathways in breast cancer for use in discovery of new biomarkers for diagnosis or therapeutic targets for treatment. [BMB Reports 2019; 52(2): 113-118].
Topics: Breast Neoplasms; Cysteine Endopeptidases; Female; Humans; Peptide Hydrolases; Protein Processing, Post-Translational; Signal Transduction; Small Ubiquitin-Related Modifier Proteins; Sumoylation
PubMed: 30638182
DOI: 10.5483/BMBRep.2019.52.2.017 -
Molecular and Cellular Biology Mar 2021The nuclear and subnuclear compartmentalization of the telomerase-associated protein and H/ACA ribonucleoprotein component dyskerin is an important although incompletely...
The nuclear and subnuclear compartmentalization of the telomerase-associated protein and H/ACA ribonucleoprotein component dyskerin is an important although incompletely understood aspect of H/ACA ribonucleoprotein function. Four SUMOylation sites were previously identified in the C-terminal nuclear/nucleolar localization signal (N/NoLS) of dyskerin. We found that a cytoplasmic localized C-terminal truncation variant of dyskerin lacking most of the C-terminal N/NoLS represents an under-SUMOylated variant of dyskerin compared to wild-type dyskerin. We demonstrate that mimicking constitutive SUMOylation of dyskerin using a SUMO3 fusion construct can drive nuclear accumulation of this variant and that the SUMO site K467 in this N/NoLS is particularly important for the subnuclear localization of dyskerin to the nucleolus in a mature H/ACA complex assembly- and SUMO-dependent manner. We also characterize a novel SUMO-interacting motif in the mature H/ACA complex component GAR1 that mediates the interaction between dyskerin and GAR1. Mislocalization of dyskerin, either in the cytoplasm or excluded from the nucleolus, disrupts dyskerin function and leads to reduced interaction of dyskerin with the telomerase RNA. These data indicate a role for dyskerin C-terminal N/NoLS SUMOylation in regulating the nuclear and subnuclear localization of dyskerin, which is essential for dyskerin function as both a telomerase-associated protein and as an H/ACA ribonucleoprotein.
Topics: Cell Cycle Proteins; Cell Nucleus; Cytoplasm; Dyskeratosis Congenita; Humans; Nuclear Localization Signals; Nuclear Proteins; RNA; RNA-Binding Proteins; Ribonucleoproteins, Small Nucleolar; Sumoylation; Telomerase
PubMed: 33526451
DOI: 10.1128/MCB.00464-20 -
Current Genetics Jun 2017The family of RecQ helicases is evolutionary conserved from bacteria to humans and play key roles in genome stability. The budding yeast RecQ helicase Sgs1 has been... (Review)
Review
The family of RecQ helicases is evolutionary conserved from bacteria to humans and play key roles in genome stability. The budding yeast RecQ helicase Sgs1 has been implicated in several key processes during the repair of DNA damage by homologous recombination as part of the STR complex (Sgs1-Top3-Rmi1). Limited information on how is Sgs1 recruited and regulated at sites of damage is available. Recently, we and others have uncover a direct link between the Smc5/6 complex and Sgs1. Most roles of Sgs1 during recombination, including DNA end resection, Holiday junction dissolution, and crossover suppression, are regulated through Mms21-dependent SUMOylation. Smc5/6 first acts as a recruiting platform for STR and then SUMOylates STR components to regulate their function. Importantly, the assembly of STR is totally independent of Smc5/6. Here, we provide a brief overview of STR regulation by Smc5/6.
Topics: Cell Cycle Proteins; DNA Damage; DNA-Binding Proteins; Genomic Instability; Homologous Recombination; Multiprotein Complexes; RecQ Helicases; SUMO-1 Protein; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Sumoylation
PubMed: 27664093
DOI: 10.1007/s00294-016-0648-5 -
Life Science Alliance Jun 2022During infection, the human immunodeficiency virus type 1 (HIV-1) manipulates host cell mechanisms to its advantage, thereby controlling its replication or latency, and...
During infection, the human immunodeficiency virus type 1 (HIV-1) manipulates host cell mechanisms to its advantage, thereby controlling its replication or latency, and evading immune responses. Sumoylation is an essential post-translational modification that controls vital cellular activities including proliferation, stemness, or anti-viral immunity. SUMO peptides oppose pathogen replication and mediate interferon-dependent anti-viral activities. In turn, several viruses and bacteria attack sumoylation to disarm host immune responses. Here, we show that HIV-1 impairs cellular sumoylation and targets the host SUMO E1-activating enzyme. HIV-1 expression in cultured HEK293 cells or in CD4 Jurkat T lymphocytes diminishes sumoylation by both SUMO paralogs, SUMO1 and SUMO2/3. HIV-1 causes a sharp and specific decline in UBA2 protein levels, a subunit of the heterodimeric SUMO E1 enzyme, which likely serves to reduce the efficiency of global protein sumoylation. Furthermore, HIV-1-infected individuals display a significant reduction in total leukocyte sumoylation that is uncoupled from HIV-induced cytopenia. Because sumoylation is vital for immune function, T-cell expansion and activity, loss of sumoylation during HIV disease may contribute to immune system deterioration in patients.
Topics: HEK293 Cells; HIV Infections; HIV-1; Humans; Protein Processing, Post-Translational; Sumoylation; Ubiquitin-Activating Enzymes
PubMed: 35181598
DOI: 10.26508/lsa.202101103 -
Medicina 2019Post-translational modifications (PTMs) are covalent modifications in proteins during or after their synthesis. Among them, the best known are phosphorylation,... (Review)
Review
Post-translational modifications (PTMs) are covalent modifications in proteins during or after their synthesis. Among them, the best known are phosphorylation, methylation, acetylation, and also cleavage or binding of small peptides (ubiquitination, SUMOylation and NEDDylation). Often the protein is modified in multiple sites and these modifications are coordinated generating a PTMs crosstalk. Altered patterns of PTMs have been related to several pathologies. Currently, advances in mass spectrometry have made it possible to study multiple PTMs simultaneously. Oncology is one of the disciplines that incorporated these technologies for the need to better characterize tumors. In cancer, several alterations related to the ubiquitinlike PTMs have been described, such as SUMOylation. In particular, the interaction between different PTMs with SUMOylation has been studied in the context of the von Hippel Lindau (VHL) multitumoral syndrome, generating new putative biomarkers for the evolution of these tumors. RSUME or RWDD3, an enhancer of SUMOylation that acts on VHL and HIF proteins, shows a correlation with malignant parameters in this type of tumors, such as angiogenesis. Regulators of PTMs are becoming relevant as biomarkers in cancer.
Topics: Humans; Neoplasms; Phosphorylation; Protein Processing, Post-Translational; Proteome; Sumoylation; Transcription Factors; Ubiquitination
PubMed: 31864228
DOI: No ID Found -
European Review For Medical and... Apr 2017SUMOylation regulates diverse cellular processes including transcription, cell cycle, protein stability, and apoptosis. A recent research has now revealed the role of... (Review)
Review
SUMOylation regulates diverse cellular processes including transcription, cell cycle, protein stability, and apoptosis. A recent research has now revealed the role of SUMO1 in cardiac disorders. Studies have evidenced that failing heart induces SUMO2/3 conjugation. Moreover, increased SUMO2/3- dependent modification has been observed to result in congestive heart disease such as cardiac hypertrophy by promoting cardiac cell death. Also, few recent studies have confirmed the role of SUMOylation in cardiac protein degradation. On the other hand, over-expression of SENP5, SUMO2/3-specific deconjugation enzyme has been observed to result in dilated cardiomyopathy or cardiac failure. So, the present review article would enlighten the latest updates about SUMOylation and associated factors during cardiac disorders.
Topics: Apoptosis; Heart; Heart Diseases; Heart Failure; Humans; Sumoylation
PubMed: 28429347
DOI: No ID Found -
Journal of Cerebral Blood Flow and... Jan 2018Post-translational protein modification by small ubiquitin-like modifier (SUMO) regulates a myriad of homeostatic and stress responses. The SUMOylation pathway has been... (Review)
Review
Post-translational protein modification by small ubiquitin-like modifier (SUMO) regulates a myriad of homeostatic and stress responses. The SUMOylation pathway has been extensively studied in brain ischemia. Convincing evidence is now at hand to support the notion that a major increase in levels of SUMOylated proteins is capable of inducing tolerance to ischemic stress. Therefore, the SUMOylation pathway has emerged as a promising therapeutic target for neuroprotection in the face of brain ischemia. Despite this, it is prudent to acknowledge that there are many key questions still to be addressed in brain ischemia related to SUMOylation. Accordingly, herein, we provide a critical review of literature within the field to summarize current knowledge and in so doing highlight pertinent translational implications of the SUMOylation pathway in brain ischemia.
Topics: Brain Ischemia; Humans; Neuroprotection; Sumoylation
PubMed: 29148315
DOI: 10.1177/0271678X17742260