S-Nitrosylation at the active site decreases the ubiquitin-conjugating activity of ubiquitin-conjugating enzyme E2 D1 (UBE2D1), an ERAD-associated protein

Fujikawa, Kana; Nakahara, Kengo; Takasugi, Nobumasa; Nishiya, Tadashi; Ito, Akihiro; Uchida, Koji; Uehara, Takashi

doi:10.1016/j.bbrc.2020.02.011

Cited by 10 publications

(4 citation statements)

References 36 publications

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“…Numbers indicate the positions of amino acid residues. Information on PTMs was obtained from PhosphoSite ® ( Hornbeck et al, 2015 ), with the exception of S-nitrosylation of Cys85 (C85) ( Valek et al, 2019 ; Fujikawa et al, 2020 ) and phosphorylation of UBE2D3-Ser138 ( Roman-Trufero et al, 2020 ). (B) Phenotypic effects of the S138A mutation during early mouse development.…”

Section: The Ube2d Proteins Have Multiple Roles In Vertebrate Signall...mentioning

confidence: 99%

“…Another PTM that forms part of this cluster is S-nitrosylation of the active site cysteine, which has been has been reported to reduce the activity of the UBE2D enzymes, with downstream effects on CHIP/STUB1 and on the targeting of misfolded proteins by endoplasmic reticulum-associated protein degradation (ERAD) ( Valek et al, 2019 ; Fujikawa et al, 2020 ). S-nitrosylation has been implicated in pro- and anti-inflammatory effects, promotion of apoptosis and a wide range of other biological processes ( Foster et al, 2003 ; Hara et al, 2005 ; Aguilar et al, 2020 ).…”

Section: The Ube2d Proteins Have Multiple Roles In Vertebrate Signall...mentioning

confidence: 99%

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The UBE2D ubiquitin conjugating enzymes: Potential regulatory hubs in development, disease and evolution

Román-Trufero

Dillon

2022

Front. Cell Dev. Biol.

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Ubiquitination of cellular proteins plays critical roles in key signalling pathways and in the regulation of protein turnover in eukaryotic cells. E2 ubiquitin conjugating enzymes function as essential intermediates in ubiquitination reactions by acting as ubiquitin donors for the E3 ubiquitin ligase enzymes that confer substrate specificity. The members of the UBE2D family of E2 enzymes are involved in regulating signalling cascades through ubiquitination of target proteins that include receptor tyrosine kinases (RTKs) and components of the Hedgehog, TGFβ and NFκB pathways. UBE2D enzymes also function in transcriptional control by acting as donors for ubiquitination of histone tails by the Polycomb protein Ring1B and the DNA methylation regulator UHRF1 as well as having roles in DNA repair and regulation of the level of the tumour suppressor p53. Here we review the functional roles and mechanisms of regulation of the UBE2D proteins including recent evidence that regulation of the level of UBE2D3 is critical for controlling ubiquitination of specific targets during development. Cellular levels of UBE2D3 have been shown to be regulated by phosphorylation, which affects folding of the protein, reducing its stability. Specific variations in the otherwise highly conserved UBE2D3 protein sequence in amniotes and in a subgroup of teleost fishes, the Acanthomorpha, suggest that the enzyme has had important roles during vertebrate evolution.

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Section: The Ube2d Proteins Have Multiple Roles In Vertebrate Signall...mentioning

confidence: 99%

Section: The Ube2d Proteins Have Multiple Roles In Vertebrate Signall...mentioning

confidence: 99%

The UBE2D ubiquitin conjugating enzymes: Potential regulatory hubs in development, disease and evolution

Román-Trufero

Dillon

2022

Front. Cell Dev. Biol.

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“…The role of ubiquilin 1 has also been reported in the regulation of the protein quality control system and thus may have a decisive role in protein aggregation and consequently in PD pathogenesis specifically in the context of ER-related functions. Recently, it has been reported that NO-mediated S-nitrosylation of ubiquitin conjugating enzyme, UE2D1, an ERAD-associated protein that has also been reported indicating the NO-mediated ER stress induced pathological responses …”

Section: No and Endoplasmic Reticulum Stressmentioning

confidence: 99%

“…Recently, it has been reported that NO-mediated S-nitrosylation of ubiquitin conjugating enzyme, UE2D1, an ERAD-associated protein that has also been reported indicating the NO-mediated ER stress induced pathological responses. 95…”

Section: No and Endoplasmic Reticulum Stressmentioning

confidence: 99%

Updates on Versatile Role of Putative Gasotransmitter Nitric Oxide: Culprit in Neurodegenerative Disease Pathology

Singh

2020

ACS Chem. Neurosci.

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Nitric oxide (NO) is a versatile gasotransmitter that contributes in a range of physiological and pathological mechanims depending on its cellular levels. An appropriate concentration of NO is essentially required for cellular physiology; however, its increased level triggers pathological mechanisms like altered cellular redox regulation, functional impairment of mitochondrion, and modifications in cellular proteins and DNA. Its increased levels also exhibit post-translational modifications in protein through S-nitrosylation of their thiol amino acids, which critically affect the cellular physiology. Along with such modifications, NO could also nitrosylate the endoplasmic reticulum (ER)-membrane located sensors of ER stress, which subsequently affect the cellular protein degradation capacity and lead to aggregation of misfolded/unfolded proteins. Since protein aggregation is one of the pathological hallmarks of neurodegenerative disease, NO should be taken into account during development of disease therapies. In this Review, we shed light on the diverse role of NO in both cellular physiology and pathology and discussed its involvement in various pathological events in the context of neurodegenerative diseases.

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Methamphetamine-induced dopaminergic neurotoxicity as a model of Parkinson’s disease

et al. 2021

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S-Nitrosylation at the active site decreases the ubiquitin-conjugating activity of ubiquitin-conjugating enzyme E2 D1 (UBE2D1), an ERAD-associated protein

Cited by 10 publications

References 36 publications

The UBE2D ubiquitin conjugating enzymes: Potential regulatory hubs in development, disease and evolution

The UBE2D ubiquitin conjugating enzymes: Potential regulatory hubs in development, disease and evolution

Updates on Versatile Role of Putative Gasotransmitter Nitric Oxide: Culprit in Neurodegenerative Disease Pathology

Methamphetamine-induced dopaminergic neurotoxicity as a model of Parkinson’s disease

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