Sumoylation Modulates the Susceptibility to Type 1 Diabetes

Zhang, Jing; Chen, Zhishui; Zhou, Zhiguang; Yang, Ping; Wang, Cong Yi

doi:10.1007/978-3-319-50044-7_18

Cited by 18 publications

(13 citation statements)

References 199 publications

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“…[3,7] SUMO-2 and SUMO-3 are mainly present in the nucleoplasm in a free state and only bind to substrates to exert corresponding functions after cells are stimulated. [8–10] SUMO-1, SUMO-2, and SUMO-3 all exhibit high expression levels in various types of tissues and organs. However, SUMO-4 exhibits a low level of expression in tissues, such as the kidney, spleen, and lymph nodes.…”

Section: Sumosmentioning

confidence: 99%

“…However, SUMO-4 exhibits a low level of expression in tissues, such as the kidney, spleen, and lymph nodes. [10] SUMO-4 was first discovered in an analysis of single nucleotide polymorphisms associated with type 1 diabetes mellitus. [10] It exhibits low expression levels under physiological conditions and rarely binds to substrate proteins, while its expression significantly increases when cells are subjected to oxidative stress and hypoxic injury.…”

Section: Sumosmentioning

confidence: 99%

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Progress of small ubiquitin-related modifiers in kidney diseases

et al. 2019

Chinese Medical Journal

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Objective: Small ubiquitin-related modifiers (SUMOs) are a group of post-translational modification proteins extensively expressed in eukaryotes. Abnormal SUMOylation can lead to the development of various diseases. This article summarizes the progress on research of the role of SUMOs in various types of kidney diseases to further increase the understanding of the regulatory functions of SUMOylation in the pathogenesis of kidney diseases. Data sources: This review was based on articles published in the PubMed databases up to January 2018, using the keywords including “SUMOs,” “SUMOylation,” and “kidney diseases.” Study selection: Original articles and critical reviews about SUMOs and kidney disease were selected for this review. A total of 50 studies were in English. Results: SUMO participates in the activation of NF-κB inflammatory signaling pathway, playing a central regulatory role in the inflammation and progression of DN, and the secretion of various chemokines in AKI. SUMO involves in the regulation of TG2 and Nrf2 antioxidant stress, affecting renal tubular injury in AKI. SUMO affects the MAPK/ERK pathway, regulating intracellular signal transduction, modulating the transcription and expression of effector molecules in DN. SUMO contributes to the TGF-β/Smad pathway, leading to fibrosis of the kidney. The conjugate combination of SUMO and p53 regulates cell proliferation and apoptosis, and participates in the regulation of tumorigenesis. In addition, SUMOylation of MITF modulates renal tumors secondary to melanoma, Similarly, SUMOylation of tumor suppressor gene VHL regulates the occurrence of renal cell carcinoma in VHL syndrome. Conclusions: Tissue injury, inflammatory responses, fibrosis, apoptosis, and tumor proliferation in kidney diseases all involve SUMOs. Further research of the substrate SUMOylation and regulatory mechanisms of SUMO in kidney diseases will improve and develop new treatment measures and strategies targeting kidney diseases.

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Section: Sumosmentioning

confidence: 99%

Section: Sumosmentioning

confidence: 99%

Progress of small ubiquitin-related modifiers in kidney diseases

et al. 2019

Chinese Medical Journal

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“…The post‐translational modification of proteins through the addition of small ubiquitin‐like modifier (SUMO) proteins regulates a broad range of cellular functions including mitosis, cell differentiation, and synaptic transmission (Deyrieux & Wilson, ; Gwizdek, Casse, & Martin, ; Henley, Craig, & Wilkinson, ; Mukhopadhyay & Dasso, ). SUMOs have thus been implicated in several disease states such as cancer, diabetes, cardiovascular disease, and neurological disorders (Abe et al, ; Eifler & Vertegaal, ; Henley et al, ; Lee, Choi, & Baek, ; Zhang, Chen, Zhou, Yang, & Wang, ). SUMOs are covalently attached to target proteins by conjugating enzymes in a process called SUMOylation.…”

Section: Introductionmentioning

confidence: 99%

Synaptic localization of the SUMOylation‐regulating protease SENP5 in the adult mouse brain

Akiyama

Nakadate

Sakakibara

2018

J of Comparative Neurology

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Covalent conjugation of small ubiquitin-like modifiers (SUMOs) or SUMOylation is a reversible post-translational modification that regulates the stability and function of target proteins. SUMOs are removed from substrate proteins by sentrin/SUMO-specific proteases (SENPs). Numerous studies have implicated SUMOylation in various physiological and pathological processes in neurons. To understand the functional roles of SUMOylation, it is necessary to determine the distribution of enzymes regulating SUMO conjugation and deconjugation; yet, the localization of SENPs has not been described in detail in intact brain tissue. Here, we report the distribution and subcellular localization of SENP3 and 5 in the adult murine brain. Immunohistochemical analyses revealed the ubiquitous distribution of both SENPs across different brain regions. Within individual cells, SENP3 was confined to the nucleus, consistent with the conventional view that SENPs regulate nuclear events. In contrast, SENP5 was detected in the neuropil but not in cell bodies. Moreover, strong SENP5 immunoreactivity was observed in regions with high numbers of synapses such as the cerebellar glomeruli, suggesting that SENP5 localizes to pre- and/or postsynaptic structures. We performed double immunolabeling in cultured neurons and found that SENP5 co-localized with pre- and post-synaptic markers, as well as a mitochondrial marker. Immunoelectron microscopy confirmed this finding and revealed that SENP5 was localized to presynaptic terminals, postsynaptic spines, and mitochondria in axon terminals. These findings advance the current understanding of the functional roles of SUMOylation in neurons, especially in synaptic regulation, and have implications for future therapeutic strategies in neurodegenerative disorders mediated by mitochondrial dysfunction.

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“…Among which, SUMOylation, one of the reversible posttranslational modifications, has recently been noted to play a critical role in the regulation of cellular processes including gene transcription, protein localization, DNA repair and cell cycle progression [29,30]. Importantly, a wellbalanced SUMOylation in substrates is essential for normal cellular behaviors, and altered SUMOylation predisposes to the risk for developing a large number of diseases such as cancer, neurodegenerative disorders (e.g., Alzheimer's, Parkinson's, and Huntington's disease), diabetes and so on [31][32][33][34][35][36]. However, the exact impact of SUMOylation on the regulation of airway inflammation and epithelial damage in smoking subjects remains almost completely unknown.…”

Section: Discussionmentioning

confidence: 99%

Cigarette smoke extract stimulates bronchial epithelial cells to undergo a SUMOylation turnover

Zhou

Zhang

et al. 2020

BMC Pulm Med

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Background Chronic obstructive pulmonary disease (COPD) characterized by the airway and lung inflammation, is a leading cause of morbidity and mortality worldwide, especially among smokers over 40 years of age and individuals exposed to biomass smoke. Although the detailed mechanisms of this disease remain elusive, there is feasible evidence that protein posttranslational modifications (PTMs) may play a role in its pathoetiology. We thus conducted studies to dissect the effect of cigarette smoke extracts (CSE) on the change of SUMOylated substrates in human bronchial epithelial cells (HBEs). Methods Samples were collected in HBEs with or without 24 h of CSE insult and then subjected to Western-blot and LC-MS/MS analysis. Subsequently, bioinformatic tools were used to analyze the data. The effect of SUMOylation on cytochrome P450 1A1 (CYP1A1) was evaluated by flow cytometry. Results It was noted that CSE stimulated HBEs to undergo a SUMOylation turnover as evidenced by the changes of SUMOylated substrates and SUMOylation levels for a particular substrate. The SUMOylated proteins are relevant to the regulation of biological processes, molecular function and cellular components. Particularly, CSE stimulated a significant increase of SUMOylated CYP1A1, a critical enzyme involved in the induction of oxidative stress. Conclusions Our data provide a protein SUMOylation profile for better understanding of the mechanisms underlying COPD and support that smoking induces oxidative stress in HBEs, which may predispose to the development of COPD in clinical settings.

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Sumoylation Modulates the Susceptibility to Type 1 Diabetes

Cited by 18 publications

References 199 publications

Progress of small ubiquitin-related modifiers in kidney diseases

Progress of small ubiquitin-related modifiers in kidney diseases

Synaptic localization of the SUMOylation‐regulating protease SENP5 in the adult mouse brain

Cigarette smoke extract stimulates bronchial epithelial cells to undergo a SUMOylation turnover

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