Eun Kyung Lee

Bio: Eun Kyung Lee is an academic researcher from Inha University. The author has contributed to research in topics: Protein aggregation & Proinflammatory cytokine. The author has an hindex of 6, co-authored 8 publications receiving 349 citations.

Smad7 binds to the adaptors TAB2 and TAB3 to block recruitment of the kinase TAK1 to the adaptor TRAF2.

Abstract: Transforming growth factor-beta1 (TGF-beta1) regulates inflammation and can inhibit activation of the transcription factor NF-kappaB in certain cell types. Here we show that the TGF-beta-induced signaling protein Smad7 bound to TAB2 and TAB3, which are adaptors that link the kinase TAK1 to 'upstream' regulators in the proinflammatory tumor necrosis factor (TNF) signaling pathway. Smad7 thereby promoted TGF-beta-mediated anti-inflammatory effects. The formation of Smad7-TAB2 and Smad7-TAB3 complexes resulted in the suppression of TNF signaling through the adaptors TRAF2, TAB2 and/or TAB3, and TAK1. Furthermore, expression of a transgene encoding Smad7 in mouse skin suppressed inflammation and NF-kappaB nuclear translocation substantially and disrupted the formation of endogenous TRAF2-TAK1-TAB2 and TRAF2-TAK1-TAB3 complexes. Thus, Smad7 is a critical mediator of TGF-beta signals that block proinflammatory TNF signals.

Smad6 negatively regulates interleukin 1-receptor-Toll-like receptor signaling through direct interaction with the adaptor Pellino-1.

Abstract: Transforming growth factor-beta1 (TGF-beta1) is a potent cytokine with pleiotropic effects, including anti-inflammatory activity. Here we show that the signaling protein Smad6 bound to Pellino-1, an adaptor protein of mammalian interleukin 1 receptor (IL-1R)-associated kinase 1 (IRAK1), and thereby promoted TGF-beta-mediated anti-inflammatory effects. Smad6-Pellino-1 interaction abrogated signaling mediated by a complex of IRAK1, Pellino-1 and adaptor protein TRAF6 that formed after stimulation by IL-1beta treatment. Blockade of IRAK1-Pellino-1-TRAF6 signaling prevented degradation of the inhibitor IkappaBalpha and subsequent nuclear translocation of transcription factor NF-kappaB and thus expression of proinflammatory genes. 'Knockdown' of endogenous Smad6 expression by RNA interference reduced anti-inflammatory activity mediated by TGF-beta1 or the TGF-beta family member BMP-4. Thus Smad6 is a critical mediator of the TGF-beta-BMP pathway that mediates anti-inflammatory activity and negatively regulates IL-1R-Toll-like receptor signals.

Self‐oligomerization and protein aggregation of α‐synuclein in the presence of Coomassie Brilliant Blue

Abstract: α-Synuclein has been implicated in various neurodegenerative disorders, including Parkinson's and Alzheimer's diseases, by its participation in abnormal protein depositions. As the protein has been suggested to play a significant role in the formation of the deposits which might be responsible for neurodegeneration, there is a strong demand to screen for α-synuclein-interactive small molecules. In this report, Coomassie Brilliant Blue (CBB) interaction of α-synuclein has been investigated with respect to induction of protein self-oligomerization in the presence of the chemical coupling reagent N-(ethoxycarbonyl)-2-ethoxy-1,2-dihydroquinoline. Both CBB-G and CBB-R, which differ by only two methyl groups, induced the self-oligomerization of α-synuclein in a biphasic manner with optimal dye concentrations of 250 µm and 150 µm, respectively. The protein aggregates of α-synuclein induced by the dyes in the absence of the coupling reagent were analysed by electron microscopy. Whereas CBB-G induced formation of protein aggregates with a worm-like structure, CBB-R induced clear fibrilization of α-synuclein on a background of granular structures. CBB-R interacted with α-synuclein approximately twice as effectively as CBB-G (dissociation constants 0.63 µm and 1.37 µm, respectively). These dye interactions were independent from the acidic C-terminus of α-synuclein, which was reminiscent of the Αβ25–35 interaction of α-synuclein. However, the metal-catalysed oxidative self-oligomerization of α-synuclein in the presence of Cu2+/H2O2, which was augmented synergistically by Αβ25–35, was not affected by the dyes. This indicates that the dye binding site is also distinctive from the Αβ25–35 interaction site on α-synuclein. These biochemically specific interactions between α-synuclein and the dyes indicate that α-synuclein-interactive small molecules could provide a tool with which to approach development of diagnostic, preventive, or therapeutic strategies for various α-synuclein-related neurodegenerative disorders.

Metals in Neurobiology: Probing Their Chemistry and Biology with Molecular Imaging

Abstract: The brain is a singular organ of unique biological complexity that serves as the command center for cognitive and motor function. As such, this specialized system also possesses a unique chemical composition and reactivity at the molecular level. In this regard, two vital distinguishing features of the brain are its requirements for the highest concentrations of metal ions in the body and the highest per-weight consumption of body oxygen. In humans, the brain accounts for only 2% of total body mass but consumes 20% of the oxygen that is taken in through respiration. As a consequence of high oxygen demand and cell complexity, distinctly high metal levels pervade all regions of the brain and central nervous system. Structural roles for metal ions in the brain and the body include the stabilization of biomolecules in static (e.g., Mg2+ for nucleic acid folds, Zn2+ in zinc-finger transcription factors) or dynamic (e.g., Na+ and K+ in ion channels, Ca2+ in neuronal cell signaling) modes, and catalytic roles for brain metal ions are also numerous and often of special demand.

MicroRNA-155 modulates the interleukin-1 signaling pathway in activated human monocyte-derived dendritic cells

Abstract: In response to inflammatory stimulation, dendritic cells (DCs) have a remarkable pattern of differentiation (maturation) that exhibits specific mechanisms to control immunity. Here, we show that in response to Lipopolysaccharides (LPS), several microRNAs (miRNAs) are regulated in human monocyte-derived dendritic cells. Among these miRNAs, miR-155 is highly up-regulated during maturation. Using LNA silencing combined to microarray technology, we have identified the Toll-like receptor/interleukin-1 (TLR/IL-1) inflammatory pathway as a general target of miR-155. We further demonstrate that miR-155 directly controls the level of TAB2, an important signal transduction molecule. Our observations suggest, therefore, that in mature human DCs, miR-155 is part of a negative feedback loop, which down-modulates inflammatory cytokine production in response to microbial stimuli.