이기영 교수

Activation of the transcription factor NF-kappaB after engagement of the T cell receptor (TCR) is important for T cell proliferation and activation during the adaptive immune response. Recent reports have elucidated a signaling pathway that involves the protein kinase C (PKC), the scaffold protein CARD11 (also called CARMA-1), the caspase recruitment domain (CARD)-containing protein Bcl10, and the paracaspase (protease related to caspases) MALT1 as critical intermediates linking the TCR to the I

3-MA: 3-methyladenine; BECN1: beclin 1; CHUK/IKKA: conserved helix-loop-helix ubiquitous kinase; ECSIT: ECSIT signalling integrator; ELISA: enzyme-linked immunosorbent assay; NFKB: nuclear factor kappa-light-chain-enhancer of activated B cells; IB: immunoblotting; IKBKB/IKKB: inhibitor of nuclear factor kappa B kinase subunit beta; IL1B: interleukin 1 beta; IL6: interleukin 6; IP: immunoprecipitation; LPS: lipopolysaccharide; MAP1LC3/LC3: microtuble associated protein 1 light chain 3; MAP3K7/TAK

We report a novel function of peroxiredoxin-1 (Prx-1) in the ASK1-mediated signaling pathway. Prx-1 interacts with ASK1 via the thioredoxin-binding domain of ASK1 and this interaction is highly inducible by H2O2. However, catalytic mutants of Prx1, C52A, C173A, and C52A/C173A, could not undergo H2O2 inducible interactions, indicating that the redox-sensitive catalytic activity of Prx-1 is required for the interaction with ASK1. Prx-1 overexpression inhibited the activation of ASK1, and resulted

Oxidative stress is implicated in the pathogenesis of allergic asthma and remains an attractive target for the prevention of the disease. Herein, we investigated the anti‐inflammatory effects of apocynin, a NADPH oxidase (NOX) inhibitor, in both in vitro and in vivo allergen‐induced experimental asthma mediated by Th2 hyperresponsiveness. Apocynin showed potential antioxidant activities and inhibitory effects on the activation of redox‐sensitive transcription factors, such as NF‐κB and AP‐1, ind

ECSIT (evolutionarily conserved signaling intermediate in Toll pathways) is known as a multifunctional regulator in different signals, including Toll-like receptors (TLRs), TGF-β, and BMP. Here, we report a new regulatory role of ECSIT in TLR4-mediated signal. By LPS stimulation, ECSIT formed a high molecular endogenous complex including TAK1 and TRAF6, in which ECSIT interacted with each protein and regulated TAK1 activity, leading to the activation of NF-κB. ECSIT-knockdown THP-1 (ECSIT(KD) TH

KRAS homo-dimerization has been implicated in the activation of RAF kinases, however, the mechanism and structural basis remain elusive. We developed a system to study KRAS dimerization on nanodiscs using paramagnetic relaxation enhancement (PRE) NMR spectroscopy, and determined distinct structures of membrane-anchored KRAS dimers in the active GTP- and inactive GDP-loaded states. Both dimerize through an α4-α5 interface, but the relative orientation of the protomers and their contacts differ su

The tumor suppressor retinoblastoma protein (RB) plays a central role in cellular growth regulation, differentiation, and apoptosis. Phosphorylation of RB results in a consequent loss of its ability to inhibit cell cycle progression. However, how RB phosphorylation might be regulated in apoptotic or postmitotic cells, such as neurons, remains unclear. Here we report that neuronal Cdc2-like kinase (Nclk), composed of Cdk5 and a neuronal Cdk5 activator (p25(nck5a)), can bind and phosphorylate RB.

Salt-inducible kinases (SIKs) are a family of related serine-threonine kinases and are involved in controlling various metabolisms such as liver glucose homeostasis, hepatic lipogenesis, steroidogenesis, and adipogenesis. Here we investigated the regulatory role of SIK proteins in Toll-like receptor 4 (TLR4)-mediated signaling. Overexpression of SIK1 and SIK3, but not SIK2, significantly inhibited nuclear factor-κB activity in response to lipopolysaccharide stimulation and affected the expressio

Ubiquitin-specific protease 14 (USP14), one of three proteasome-associated deubiquitinating enzymes, has multifunctional roles in cellular context. Here, we report a novel molecular mechanism and function of USP14 in regulating autophagy induction and nuclear factor-kappa B (NF-κB) activation induced by toll-like receptor (TLR) 4 (TLR4). USP14 interacted with tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) and interrupted the association of Beclin 1 with TRAF6, leading to inhibi

A TRAF6-ECSIT complex is crucial for the generation of mitochondrial reactive oxygen species (mROS) and nuclear factor-kappa B (NF-κB) activation induced by Toll-like receptor 4 (TLR4). Peroxiredoxin-6 (Prdx6) as a member of the peroxiredoxin family of antioxidant enzymes is involved in antioxidant protection and cell signaling. Here, we report on a regulatory role of Prdx6 in mROS production and NF-κB activation by TLR4. Prdx6 was translocated into the mitochondria by TLR4 stimulation and Prdx6

Our results suggest that FFAR2 signaling antagonized TLR2- and TLR3-induced lung cancer progression via the suppression of the cAMP-AMPK-TAK1 signaling axis for the activation of NF-κB, and its agonist might be a potential therapeutic agent for the treatment of lung cancer.

Toll-like receptors (TLRs) induce the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and autophagy through the TNF (Tumor necrosis factor) receptor-associated factor 6 (TRAF6)-evolutionarily conserved signaling intermediate in Toll pathways (ECSIT) and TRAF6-BECN1 signaling axes, respectively. Having shown that p62 negatively regulates Toll-like receptor 4 (TLR4)-mediated signaling via TRAF6-ECSIT signaling axis, we herein investigated whether p62 is functio

Cereblon (CRBN) as a multifunctional protein has been extensively studied. Here, we show that CRBN is a negative regulator of bactericidal activity and autophagy activation. Mitochondrial localization of CRBN was significantly increased in response to Toll-like receptor 4 (TLR4) stimulation. CRBN interrupted the association of evolutionarily conserved signaling intermediate in Toll pathways (ECSIT)-TNF-receptor associated factor 6 (TRAF6) complex, thereby inhibiting the ubiquitination of ECSIT,