The Role of Ubiquitination and Sumoylation in Diabetic Nephropathy

Gao, Chenlin; Huang, Wei; Kanasaki, Keizo; Xu, Yong

doi:10.1155/2014/160692

Cited by 54 publications

(56 citation statements)

References 78 publications

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“…Studies have demonstrated that ubiquitination and degradation of the target protein are involved in renal diseases including DN (43). For example, when various inflammatory cytokines were activated during DN, inhibitory-B, a protein suppressed by NFB, was degraded by the UPS, and this allowed the nuclear translocation of NFB for participation in gene transcription (44).…”

Section: Discussionmentioning

confidence: 99%

HRD1-Mediated IGF-1R Ubiquitination Contributes to Renal Protection of Resveratrol in db/db Mice

Yan

Huang

et al. 2016

Molecular Endocrinology

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Many studies have provided evidence to demonstrate the beneficial renal effects of resveratrol (RESV) due to its antioxidant character and its capacity for activation of surtuin 1. However, the molecular mechanisms underlying the protective role of RESV against kidney injury are still incompletely understood. The present study used Lepr db/db (db/db) and Lepr db/m (db/m) mice as models to evaluate the effect of RESV on diabetic nephropathy (DN). RESV reduced proteinuria and attenuated the progress of renal fibrosis in db/db mice. Treatment with RESV markedly attenuated the diabetes-induced changes in renal superoxide dismutase copper/zinc, superoxide dismutase manganese, catalase, and malonydialdehyde as well as the renal expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), α-smooth muscle actin (α-SMA), and E-cadherin in db/db mice. The kidney expression of the IGF-1 receptor (IGF-1R) was increased in db/db mice, but the expression of 3-hydroxy-3-methylglutaryl reductase degradation (HRD1), a ubiquitin E3 ligase, was significantly decreased in the DN model. RESV treatment dramatically decreased IGF-1R and increased HRD1 expressions, consistent with data obtained with HKC-8 cells. HRD1 physically interacted with IGF-1R in HKC-8 cells and liquid chromatography and tandem mass spectrometry (LC-MS/MS) data supported the concept that IGF-1R is one of the HRD1 substrates. HRD1 promoted the IGF-1R ubiquitination for degradation in HKC-8 cells, and the down-regulation of HRD1 reversed the protective effects of RESV in HKC-8 cells. In summary, we have demonstrated that RESV reduces proteinuria and attenuates the progression of renal fibrosis in db/db mice. These protective effects of RESV on DN were associated with the up-regulation of HRD1, induced by RESV, and the promotion of IGF-1R ubiquitination and degradation.

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Section: Discussionmentioning

confidence: 99%

HRD1-Mediated IGF-1R Ubiquitination Contributes to Renal Protection of Resveratrol in db/db Mice

Yan

Huang

et al. 2016

Molecular Endocrinology

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“…Protein ubiquitination and SUMOylation are vital post-translational modifications in numerous signaling pathways36373839. The ubiquitination reaction consists of the covalent attachment of ubiquitin (an 8-kDa polypeptide) to lysine residues in target proteins4041.…”

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confidence: 99%

Suppression of Rac1 Signaling by Influenza A Virus NS1 Facilitates Viral Replication

Jiang

Sheng

et al. 2016

Sci Rep

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Influenza A virus (IAV) is a major human pathogen with the potential to become pandemic. IAV contains only eight RNA segments; thus, the virus must fully exploit the host cellular machinery to facilitate its own replication. In an effort to comprehensively characterize the host machinery taken over by IAV in mammalian cells, we generated stable A549 cell lines with over-expression of the viral non-structural protein (NS1) to investigate the potential host factors that might be modulated by the NS1 protein. We found that the viral NS1 protein directly interacted with cellular Rac1 and facilitated viral replication. Further research revealed that NS1 down-regulated Rac1 activity via post-translational modifications. Therefore, our results demonstrated that IAV blocked Rac1-mediated host cell signal transduction through the NS1 protein to facilitate its own replication. Our findings provide a novel insight into the mechanism of IAV replication and indicate new avenues for the development of potential therapeutic targets.

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“…This cascade begins with the E1 activating enzyme and ends with the E3 ligating enzyme that leads to the conjugation of SUMO to lysine residues on target proteins 14 . Several SUMO E3 ligases have been identified including protein inhibitor of activated STAT (PIAS) family (PIAS1, PIAS2(x), PIAS3, PIAS4(y)), Polycomb-2 protein (Pc2), and RanBP2/Nup358 12 .…”

Section: Sumoyation – Dynamic Post-translational Modificationmentioning

confidence: 99%

“…Abnormalities in the endothelial, vascular smooth muscle, and myocardial functions caused by the pathological insults of hyperglycemia and oxidative stress in diabetes are thought to accelerate the development of cardiovascular diseases 11 . Numerous kinase signaling pathways are shared in DM and CVD pathology, several of which are heavily regulated by post-translational modifications (PTMs) 12 . In this review, we focus on the role of a dynamic PTM known as SUMOylation and its role in regulating certain kinase networks to provide a mechanistic link between DM and CVD.…”

Section: Introductionmentioning

confidence: 99%

Kinase-SUMO networks in diabetes-mediated cardiovascular disease

Chang

Abe

2016

Metabolism

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Type II diabetes mellitus (DM) is a common comorbidity in patients with cardiovascular disease (CVD). Epidemiological studies including the Framingham, UKPDS, and MRFIT studies have shown diabetes to be an independent risk factor for cardiovascular disease associated with increased incidence of morbidity and mortality. However, major randomized controlled clinical trials including ADVANCE, VAD, and ACCORD have failed to demonstrate a significant reduction in CVD complications from longstanding DM with strict glycemic control. This suggests that despite the strong clinical correlation between DM and CVD, the precise mechanisms of DM-mediated CVD pathogenesis remain unclear. Signal transduction investigations have shed some light on this question with numerous studies demonstrating the role of kinase pathways in facilitating DM and CVD pathology. Abnormalities in endothelial, vascular smooth muscle, and myocardial function from the pathological insults of hyperglycemia and oxidative stress in diabetes are thought to accelerate the development of cardiovascular disease. Extensive interplay between kinase pathways that regulate the complex pathology of DM-mediated CVD is heavily regulated by a number of post-translational modifications (PTMs). In this review, we focus on the role of a dynamic PTM known as SUMOylation and its role in regulating these kinase networks to provide a mechanistic link between DM and CVD.

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The Role of Ubiquitination and Sumoylation in Diabetic Nephropathy

Cited by 54 publications

References 78 publications

HRD1-Mediated IGF-1R Ubiquitination Contributes to Renal Protection of Resveratrol in db/db Mice

HRD1-Mediated IGF-1R Ubiquitination Contributes to Renal Protection of Resveratrol in db/db Mice

Suppression of Rac1 Signaling by Influenza A Virus NS1 Facilitates Viral Replication

Kinase-SUMO networks in diabetes-mediated cardiovascular disease

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