English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Salubrinal is a selective inhibitor of cellular complexes that dephosphorylate eukaryotic translation initiation factor 2α (eIF2α). In previous reports, salubrinal was shown to have the potential to inhibit the activation of nuclear factor-κB (NF-κB) by several stimuli. However, the effects of salubrinal on NF-κB signaling are largely unknown. In this study, we investigated whether and how salubrinal affects NF-κB activation induced by tumor necrosis factor (TNF)-α and interleukin (IL)-1β. We found that salubrinal selectively blocked TNF-α- but not IL-1β-induced activation of NF-κB. This inhibitory effect occurred upstream of transforming growth factor (TGF)-β-activated kinase 1 (TAK1). Further experiments revealed that salubrinal blocked TNF-α-triggered NF-κB activation independent of its action on eIF2α because knockdown of eIF2α by small interfering RNA (siRNA) did not reverse the inhibitory effect of salubrinal on NF-κB. Moreover, guanabenz, a selective inhibitor of the regulatory subunit of protein phosphatase (PP) 1, also preferentially inhibited TNF-α-triggered activation of NF-κB. These findings raise the possibility that salubrinal may selectively block TNF-α-triggered activation of the NF-κB pathway through inhibition of the PP1 complex.

eIF2α-Independent Inhibition of TNF-α-Triggered NF-κB Activation by Salubrinal