TRANSIENT IKK ACTIVITY MEDIATES NF-κB TEMPORAL DYNAMICS IN RESPONSE TO A WIDE RANGE OF TNFα DOSES Raymond Cheong, Adriel Bergmann, Shannon L. Werner, Joshua Regal, Alexander Hoffmann, Andre Levchenko From the 1 Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218 and the 2 Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of Califo...

Following pathogen infection, the IκB kinase (IKK)-related kinases TBK1 and IKKi phosphorylate and activate members of the Interferon Regulatory Factor transcription factors that control the transcription of a repertoire of genes with anti-viral activity. Studies have revealed that these kinases also target NF-κB and c-Jun transcription factors thereby suggesting that they could also control in...

Abstract The IκB kinase (IKK) complex plays a vital role in regulating the NF-κB activation. Aberrant activation is involved various inflammatory diseases. Thus, targeting IKK an ideal therapeutic strategy to cure and prevent diseases related In previous study, we demonstrated that IKK-interacting protein (IKIP) inhibits phosphorylation of IKKα/β through disruption formation complex. this ident...

The effect of acanthoic acid analogs on the response to proinflammatory challenge was investigated. Some pimarane diterpenes are known activators of the LXRαβ nuclear receptors, but we show here that they also exert a rapid, potent, and selective activation of the p110γ and p110δ subunits of PI3K. Combination of these effects results in an important attenuation of the global transcriptional res...

background and objectives: silymarin is a unique flavonoid complex with documented hepatoprotective properties. silybum  marianum hairy root culture as a source for producing silymarin has been an important strategy for study the cell signaling pathway. in the present investigation trichoderma strains- silybum marianum hairy root cultures interactions have been studied. methods: the effects of ...

The noncanonical IKK family member TANK-binding kinase 1 (TBK1) is activated by pro-inflammatory cytokines, but its role in controlling metabolism remains unclear. Here, we report that the kinase uniquely controls energy metabolism. Tbk1 expression is increased in adipocytes of HFD-fed mice. Adipocyte-specific TBK1 knockout (ATKO) attenuates HFD-induced obesity by increasing energy expenditure;...

Plexins are widely expressed transmembrane proteins that mediate the cellular effects of semaphorins. The molecular mechanisms of plexin-mediated signal transduction are still poorly understood. Here we show that signalling via B-family plexins leading to the activation of the small GTPase RhoA requires activation of the IκB kinase (IKK)-complex. In contrast, plexin-B-dependent regulation of R-...

One of the major attendant complications of multiple myeloma is renal injury, which contributes significantly to morbidity and mortality in this disease. Monoclonal immunoglobulin free light chains (FLCs) are usually directly involved, and tubulointerstitial renal injury and fibrosis are prominent histologic features observed in myeloma. The present study examined the role of monoclonal FLCs in...

RASSF2 belongs to the Ras-association domain family (RASSF) of proteins, which may be involved in the Hippo signalling pathway. However, the role of RASSF2 in vivo is unknown. Here, we show that Rassf2 knockout mice manifest a multisystemic phenotype including haematopoietic anomalies and defects in bone remodelling. Bone marrow (BM) transplantation showed that Rassf2(-/-) BM cells had a normal...

Volatile anesthetics modulate endothelial cell apoptosis and inhibit nuclear factor-κB (NF-κB) signaling. In this study, we aimed to assess whether desflurane preconditioning protects human umbilical vein endothelial cells (HUVECs) agaist anoxia/reoxygenation (A/R) injury. HUVECs were pre-conditioned with desflurane (1.0 MAC) for 30 min, followed by a 15-min washout, then exposed to 60 min anox...