NF-κB signaling and cell-fate decision induced by a fast-dissociating tumor necrosis factor mutant

Yin, Ningbei; Guo, Annan; Zhang, Qi; Zhang, Yalei; Xu, Youjun; Liu, Hongbo; Tang, Bo; Lai, Luhua

doi:10.1016/j.bbrc.2017.05.149

Cited by 8 publications

(11 citation statements)

References 20 publications

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“…SK‐N‐AS (human S‐type neuroblastoma, CRL‐2137™, ATCC, Rockefeller, MA, USA) cells were prepared as described before . The cells were stimulated with 1 ng·mL −1 WT‐TNFα with 1 mg·mL −1 BSA, either with or without peptides of 50 μ m .…”

Section: Methodsmentioning

confidence: 99%

“…Peptides at various concentrations were incubated with TNFa (5 ngÁmL À1 ). The mixtures were then injected to flow cell at 50 lLÁmin À1 with 60-s association period and 60-s disassociation Cell imaging and image analyses SK-N-AS (human S-type neuroblastoma, CRL-2137 TM , ATCC, Rockefeller, MA, USA) cells were prepared as described before [29]. The cells were stimulated with 1 ngÁmL À1 WT-TNFa with 1 mgÁmL À1 BSA, either with or without peptides of 50 lM.…”

Section: Spr Competitive Binding Assaymentioning

confidence: 99%

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Computational design and optimization of novel d‐peptide TNFα inhibitors

et al. 2019

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Compared to small molecule drugs, peptide therapeutics provides greater efficacy, selectivity, and safety. The intrinsic disadvantages of peptides are their sensitivity to proteases. To overcome this, we have developed a general computational strategy for de novo design of protein binding helical d‐peptides. A d‐helical fragment library was established and used in generating flexible d‐helical conformations, which were then used to generate suitable sequences with the required structural and binding properties. Using this strategy, we successfully de novo designed d‐helical peptides that bind to tumor necrosis factor‐α (TNFα), inhibit TNFα‐TNFR1 binding, reduce TNFα activity in cellular assays, and are stable against protease digestion. Our strategy of helical d‐peptide design is generally applicable for discovering d‐peptide modulators against protein–protein interactions.

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Section: Methodsmentioning

confidence: 99%

Section: Spr Competitive Binding Assaymentioning

confidence: 99%

Computational design and optimization of novel d‐peptide TNFα inhibitors

et al. 2019

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“…In this experiment, we used a SK-N-AS monoclonal stable cell line transfected with NF-κB/p65 labeled by red uorescent protein and nuclear H 2 B labeled by green uorescent were pre-incubated with 0.25 mM DMI for 1 h before stimulation with 10 ng mL -1 TNF-α at 37℃ (5% CO 2 ). The movement of NF-κB/p65 was captured every 5 min for 4 h as described before 14 . We measured the nuclear amounts of uorescent protein-RelA by time-lapse imaging adding DMI or not.…”

Section: Dimethyl Itaconate Inhibits Tnf-α-induced Nuclear Translocatmentioning

confidence: 99%

Dimethyl itaconate inhibits TNF-α induced NF-κB signaling pathway in human epithelial cells

Zhang

Deng

Hao

et al. 2020

Preprint

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Background: Dimethyl itaconate (DMI), a membrane-permeable derivative of itaconate, was found to moderate IL-17-IκBζ-induced skin pathology including psoriasis in mouse experiments . TNF-α induced NF-κB pathway, which controls a variety of immune and inflammatory responses, was also proven to play a crucial role as mediator in psoriasis. However, whether DMI interacts with the TNF-α induced NF-κB pathway remains unclear. Results: Here we show that DMI inhibits TNF-α induced NF-κB transcriptional activities in dose-dependent manner in several human cell lines using dual luciferase assay and blocks the NF-κB nuclear entry. Moreover, DMI potently inhibits IKKβ dependent phosphorylation and degradation of IκBα in TNF-α induced activation of NF-κB pathway. We also demonstrate that DMI covalently binds to cysteine residue in IKKβ, a key regulator in NF-κB pathway, to suppress IKKβ activation and inhibit the canonical NF-κB pathway. Conclusion Our study presents a new mechanism for DMI as an anti-inflammatory agent that may have therapeutic potentials in treating NF-κB related human inflammatory diseases. Our results also suggest that itaconate produced by endogenous IRG1 may regulate NF-κB at post translation modification level, and the IRG1-itaconate-NF-κB axis could be targeted as a novel strategy for the treatment of IRG1-NF-κB mediated diseases.

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“…In this experiment, we used a SK-N-AS monoclonal stable cell line transfected with NF-κB/p65 labeled by red fluorescent protein and nuclear H 2 B labeled by green fluorescent were pre-incubated with 0.25 mM DMI for 1 h before stimulation with 10 ng mL -1 TNF-α at 37℃ (5% CO 2 ). The movement of NF-κB/p65 was captured every 5 min for 4 h as described before 14 . We measured the nuclear amounts of fluorescent protein-RelA by time-lapse imaging adding DMI or not.…”

Section: Dimethyl Itaconate Inhibits Tnf-α-induced Nuclear Translocatmentioning

confidence: 99%

“…SK-N-AS cells with p65 labeled with mcherry and H 2 B labeled with EGFP which was constructed as previously described 14 were cultured in DMEM (Gibco) supplemented with 10% fetal bovine serum (FBS, Gibco) and 1% Non-Essential AminoAcid (NEAA, Gibco) in a humidified atmosphere with 5%CO 2 at 37℃.1.5x10 5 SK-N-AS cells were seeded on 35-mm glass-bottom dishes (Invitro Scientific Products, Inc.) in 3 mL medium. The day of experiment, the medium was changed to fresh DMEM containing indicated concentration of DMI.…”

Section: Nf-κb/p65 Nuclear Translocation Fluorescencementioning

confidence: 99%