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81.
82.
Seon Woo A. An Eun‐Seok Choi Wooseon Hwang Heehwa G. Son Jae‐Seong Yang Keunhee Seo Hyun‐Jun Nam Nhung T. H. Nguyen Eun Ji E. Kim Bo Kyoung Suh Youngran Kim Shunji Nakano Youngjae Ryu Chang Man Ha Ikue Mori Sang Ki Park Joo‐Yeon Yoo Sanguk Kim Seung‐Jae V. Lee 《Aging cell》2019,18(3)
PDZ domain‐containing proteins (PDZ proteins) act as scaffolds for protein–protein interactions and are crucial for a variety of signal transduction processes. However, the role of PDZ proteins in organismal lifespan and aging remains poorly understood. Here, we demonstrate that KIN‐4, a PDZ domain‐containing microtubule‐associated serine‐threonine (MAST) protein kinase, is a key longevity factor acting through binding PTEN phosphatase in Caenorhabditis elegans. Through a targeted genetic screen for PDZ proteins, we find that kin‐4 is required for the long lifespan of daf‐2/insulin/IGF‐1 receptor mutants. We then show that neurons are crucial tissues for the longevity‐promoting role of kin‐4. We find that the PDZ domain of KIN‐4 binds PTEN, a key factor for the longevity of daf‐2 mutants. Moreover, the interaction between KIN‐4 and PTEN is essential for the extended lifespan of daf‐2 mutants. As many aspects of lifespan regulation in C. elegans are evolutionarily conserved, MAST family kinases may regulate aging and/or age‐related diseases in mammals through their interaction with PTEN. 相似文献
83.
Jihun Ryu Do Un Hwang Yeon Jae Bae Si Hyeock Lee Young Ho Kim Seung‐Yeol Lee Hee‐Young Jung Kwang Shik Choi 《Entomological Research》2019,49(9):432-435
Pyrethroid insecticides have been effective and powerful for controlling mosquitoes. However, abuse of these insecticides increases the number of resistant mosquitoes. In this study, Culex pipiens pallens and Aedes koreicus were collected from an artificial reservoir in the vicinity of a populated area in Korea, which is also a migratory bird catchment area. To monitor resistance to pyrethroid insecticides in mosquitoes, genomic DNA from the collected mosquitoes was sequenced for the kdr mutation in the voltage‐gated sodium channel (VGSC) gene. As a result, three samples with homozygous resistance (17.6%) and one with heterozygous resistance (5.9%) were found among 17 Cx. pipiens pallens specimens. One of the samples had a unique sequence at the amplified VGSC region. Of the 15 Ae. koreicus, no insecticide resistant individuals were found. In Korea, this is the first report of kdr genetic traits in Ae. koreicus and Cx. pipiens pallens and of a unique VGSC allele in Cx. pipiens pallens. Further investigation is needed to monitor the kdr resistance of these species in Korea and to determine how the unique sequence found in Cx. pipiens pallens is related to insecticide resistance. 相似文献
84.
Woo Seung Son Kyu-Sung Jeong Sang Min Lim Ae Nim Pae 《Bioorganic & medicinal chemistry letters》2019,29(10):1168-1172
Highly effective and safe drugs for the treatment of neuropathic pain are urgently required and it was shown that blocking T-type calcium channels can be a promising strategy for drug development for neuropathic pain. We have developed pyrrolidine-based T-type calcium channel inhibitors by structural hybridization and subsequent assessment of in vitro activities against Cav3.1 and Cav3.2 channels. Profiling of in vitro ADME properties of compounds was also carried out. The representative compound 17h showed comparable in vivo efficacy to gabapentin in the SNL model, which indicates T-type calcium channel inhibitors can be developed as effective therapeutics for neuropathic pain. 相似文献
85.
Megan L. Machek Halie A. Sonnenschein Sasha‐Kaye I. Graham Flowreen Shikwana Seung‐Hwan L. Kim Selena Garcia DuBar Ian D. Minzer Ryan Wey Jessica K. Bell 《Protein science : a publication of the Protein Society》2019,28(8):1423-1436
Suppressor of IKKepsilon (SIKE) is a 207 residue protein that is implicated in the TLR3‐TANK‐binding kinase‐1‐mediated response to viral infection. SIKE's function in this pathway is unknown, but SIKE forms interactions with two distinct cytoskeletal proteins, α‐actinin and tubulin, and SIKE knockout reduces cell migration. As structure informs function and in the absence of solved structural homologs, our studies were directed toward creating a structural model of SIKE through biochemical and biophysical characterization to probe and interrogate SIKE function. Circular dichroism revealed a primarily (73%) helical structure of minimal stability (<Tm > =32°C) but reversibly denatured. Limited proteolysis (LP) and chemical modification identified the N‐terminal 2/3 of the protein as dynamic and accessible, whereas size exclusion chromatography (SEC) confirmed three homo‐oligomeric species. SEC coupled to chemical crosslinking characterized the primary species as dimeric, a secondary hexameric species, and a higher order aggregate/polymer. Fluorescence polarization using intrinsic tryptophan fluorescence contextualized the anisotropy value for the SIKE dimer (molecular weight 51.8 kDa) among proteins of known structure, bovine serum albumin (BSA; 66 kDa), and glutamate dehydrogenase (GDH; 332 kDa). Radii of gyration for BSA and GDH provided exclusionary values for SIKE tertiary and dimeric quaternary models that otherwise conformed to secondary structure, LP, and modification data. Dimeric quaternary models were further culled using acrylamide quenching data of SIKE's single tryptophan that showed a single, protected environment. The low cooperativity of folding and regions of dynamic and potentially disordered structure advance the hypothesis that SIKE forms a conformational ensemble of native states that accommodate SIKE's interactions with multiple, distinct protein‐binding partners. 相似文献
86.
87.
XNP/ATRX, a causative gene of X-linked alpha-thalassemia/mental retardation syndrome, encodes an SNF2 family ATPase/helicase protein. To better understand the role of XNP/ATRX in development, we isolated and characterized a Drosophila XNP/ATRX homolog, dXNP, which contains highly conserved SNF2 and helicase domains. Ectopically expressed dXNP induced strong apoptosis in the developing eye and wing, but did not affect cell cycle progression or the expression of wingless and engrailed, essential regulators of development. The dXNP-induced apoptosis was strongly suppressed by DJNKK/hemipterous mutation, and dXNP increased JNK activity. Taken together, these results suggest that dXNP regulates apoptosis via JNK activation. 相似文献
88.
Hwang J Kalinin A Hwang M Anderson DE Kim MJ Stojadinovic O Tomic-Canic M Lee SH Morasso MI 《The Journal of biological chemistry》2007,282(25):18645-18653
The novel Ca2+-binding protein, Scarf (skin calmodulin-related factor) belongs to the calmodulin-like protein family and is expressed in the differentiated layers of the epidermis. To determine the roles of Scarf during stratification, we set out to identify the binding target proteins by affinity chromatography and subsequent analysis by mass spectrometry. Several binding factors, including 14-3-3s, annexins, calreticulin, ERp72 (endoplasmic reticulum protein 72), and nucleolin, were identified, and their interactions with Scarf were corroborated by co-immunoprecipitation and co-localization analyses. To further understand the functions of Scarf in epidermis in vivo, we altered the epidermal Ca2+ gradient by acute barrier disruption. The change in the expression levels of Scarf and its binding target proteins were determined by immunohistochemistry and Western blot analysis. The expression of Scarf, annexins, calreticulin, and ERp72 were up-regulated by Ca2+ gradient disruption, whereas the expression of 14-3-3s and nucleolin was reduced. Because annexins, calreticulin, and ERp72 have been implicated in Ca2+-induced cellular trafficking, including the secretion of lamellar bodies and Ca2+ homeostasis, we propose that the interaction of Scarf with these proteins might be crucial in the process of barrier restoration. On the other hand, down-regulation of 14-3-3s and nucleolin is potentially involved in the process of keratinocyte differentiation and growth inhibition. The calcium-dependent localization and up-regulation of Scarf and its binding target proteins were studied in mouse keratinocytes treated with ionomycin and during the wound-healing process. We found increased expression and nuclear presence of Scarf in the epidermis of the wound edge 4 and 7 days post-wounding, entailing the role of Scarf in barrier restoration. Our results suggest that Scarf plays a critical role as a Ca2+ sensor, potentially regulating the function of its binding target proteins in a Ca2+-dependent manner in the process of restoration of epidermal Ca2+ gradient as well as during epidermal barrier formation. 相似文献
89.
Microsomal prostaglandin E2 synthase (mPGES-1) has been identified recently as a novel target for treating pain and inflammation. The aim of this study
is to understand the binding affinities of reported inhibitors for mPGES-1 and further to design potential new mPGES-1 inhibitors.
3D-QSAR-CoMFA (comparative molecular field analysis) and CoMSIA (comparative molecular similarity indices analysis) - techniques
were employed on a series of indole derivatives that act as selective mPGES-1 inhibitors. The lowest energy conformer of the
most active compound obtained from systematic conformational search was used as a template for the alignment of 32 compounds.
The models obtained were used to predict the activities of the test set of eight compounds, and the predicted values were
in good agreement with the experimental results. The 3D-QSAR models derived from the training set of 24 compounds were all
statistically significant (CoMFA; q
2 = 0.89, r
2 = 0.95, , and CoMSIA; q
2 = 0.84, r
2 = 0.93, , ). Contour plots generated for the CoMFA and CoMSIA models reveal useful clues for improving the activity of mPGES-1 inhibitors.
In particular, substitutions of an electronegative fluorine atom or a bulky hydrophilic phenoxy group at the meta or para positions of the biphenyl rings might improve inhibitory activity. A plausible binding mode between the ligands and mPGES-1
is also proposed. 相似文献
90.
Hiroyuki Nakamura Jong-Dae Lee Manabu Ueno Yusuke Miyajima Hyun Seung Ban 《NanoBioTechnology》2007,3(2):135-145
High accumulation and selective delivery of boron into tumor tissues are the most important requirements to achieve efficient
neutron capture therapy of cancers. We focused on liposomal boron delivery system to achieve a large amount of boron delivery
to tumor. We succeeded in the synthesis of the double-tailed boron cluster lipids 4a–c and 5a–c, which has a B12H11S-moiety as a hydrophilic function, by S-alkylation of B12H11SH with bromoacetyl and chloroacetocarbamate derivatives of diacylglycerols. Size distribution of liposomes prepared from
the boron cluster lipid 4b, dimyristoylphosphatidylcholine, polyethyleneglycol-conjugated distearoylphosphatidylethanolamine, and cholesterol was determined
as 100 nm in diameter by an electrophoretic light scattering spectrophotometer. Calcein-encapsulation experiments revealed
that these boronated liposomes are stable at 37 °C in fetal bovine serum solution for 24 h. 相似文献