Santonin-Related Compound 2 Inhibits the Nuclear Translocation of NF-\kappaB Subunit p65 by Targeting Cysteine 38 in TNF-\alpha-Induced NF-\kappaB Signaling Pathway
نویسندگان
چکیده
(11S)-2 -Bromo-3-oxoeudesmano-12,6 -lactone, designated santonin-related compound 2 (SRC2), only weakly affected I B degradation after tumor necrosis factor(TNF) stimulation, but strongly blocked the nuclear translocation of nuclear factor B (NFB) subunit p65. Replacement of Cys-38 of p65 with serine abolished the inhibitory effect of SRC2 on this TNFinduced nuclear translocation. These results indicate that SRC2 inhibits the nuclear translocation of p65 by targeting Cys-38.
منابع مشابه
The glutaredoxin/glutathione system modulates NF-kappaB activity by glutathionylation of p65 in cinnamaldehyde-treated endothelial cells.
Reversible protein glutathionylation is an important posttranslational modification that provides protection against oxidation. In endothelial cells (ECs), cinnamaldehyde is an electrophilic compound that can increase the intracellular glutathione (GSH) levels or reactive oxygen species (ROS) production depending on the treatment duration. ECs treated with GSH and H(2)O(2) show increased sulfhy...
متن کاملReactive oxygen species in tumor necrosis factor-alpha-activated primary human keratinocytes: implications for psoriasis and inflammatory skin disease.
The multifunctional cytokine tumor necrosis factor-alpha (TNF-alpha) is known to play an important role in inflammatory and immunological responses in human skin. Although it has been documented that reactive oxygen species (ROS) are involved in TNF-alpha-induced signaling pathways associated with certain inflammatory diseases, their role in TNF-alpha signaling cascades has not been examined in...
متن کاملGambogic acid, a novel ligand for transferrin receptor, potentiates TNF-induced apoptosis through modulation of the nuclear factor-kappaB signaling pathway.
Gambogic acid (GA), a xanthone derived from the resin of the Garcinia hanburyi, has been recently demonstrated to bind transferrin receptor and exhibit potential anticancer effects through a signaling mechanism that is not fully understood. Because of the critical role of NF-kappaB signaling pathway, we investigated the effects of GA on NF-kappaB-mediated cellular responses and NF-kappaB-regula...
متن کاملVaricella-zoster virus modulates NF-kappaB recruitment on selected cellular promoters.
Intercellular adhesion molecule 1 (ICAM-1) expression is down-regulated in the center of cutaneous varicella lesions despite the expression of proinflammatory cytokines such as gamma interferon and tumor necrosis factor alpha (TNF-alpha). To study the molecular basis of this down-regulation, the ICAM-1 induction of TNF-alpha was analyzed in varicella-zoster virus (VZV)-infected melanoma cells (...
متن کاملResolution of inflammation: prostaglandin E2 dissociates nuclear trafficking of individual NF-kappaB subunits (p65, p50) in stimulated rheumatoid synovial fibroblasts.
NF-kappaB transcription factors regulate inflammatory responses to cytokines such as IL-1beta and TNF-alpha. We tested whether PGE2 regulated nuclear localization of individual NF-kappaB subunits, p65 and p50, in synovial fibroblasts harvested from patients with rheumatoid arthritis (RA). IL-1beta/TNF-alpha stimulated the translocation of p65 and p50 from the cytosol to the nucleus of human RA ...
متن کامل