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991.
Mutations of the RNA-specific adenosine deaminase gene (DSRAD) are involved in dyschromatosis symmetrica hereditaria 总被引:28,自引:0,他引:28 下载免费PDF全文
Miyamura Y Suzuki T Kono M Inagaki K Ito S Suzuki N Tomita Y 《American journal of human genetics》2003,73(3):693-699
Dyschromatosis symmetrica hereditaria (DSH) (also called "reticulate acropigmentation of Dohi") is a pigmentary genodermatosis of autosomal dominant inheritance characterized by a mixture of hyperpigmented and hypopigmented macules distributed on the dorsal aspects of the hands and feet. To determine the gene responsible for this disease, we performed a genomewide search in three families with DSH and mapped the DSH locus to chromosome 1q21.3. The mutations involved in causing DSH have been identified in the gene that encodes double-stranded RNA-specific adenosine deaminase (DSRAD) as the disease gene. 相似文献
992.
The clk-1 gene was isolated from the long-lived mutant of Caenorhabditis elegans and was suggested to play a biological role in longevity (Ewbank et al., 1997, Science 275: 980-983). The primary structure of CLK-1 showed a significant homology to Saccharomyces cerevisiae Coq7p/Cat5p, which is required for the biosynthesis of ubiquinone and the derepression of gluconeogenic genes. In the present study, we isolated and characterized human and mouse orthologues of the COQ7/CLK-1 gene. Sequence analysis of both the human and the mouse COQ7 cDNAs showed an open reading frame composed of 217 amino acids with calculated molecular mass of 24,309 and 24,044 Da, respectively. Homology search revealed that human COQ7 showed 85% identity to mouse COQ7, 89% identity to rat COQ7, 53% identity to C. elegans CLK-1, and 37% identity to S. cerevisiae Coq7p/Cat5p. Zoo blot analysis implied that the COQ7 gene was well conserved among mammal, bird, and reptile genomes. Tissue blot analysis showed that human COQ7 is dominantly transcribed in heart and skeletal muscle. Genomic analyses revealed that the human COQ7 gene is composed of six exons spanning 11 kb of human genome as a single-copy gene. Radiation hybrid mapping assigned the COQ7 gene to human chromosome 16p12.3-p13.11. 相似文献
993.
N Inagaki R Maitra K Satoh H B Pakrasi 《The Journal of biological chemistry》2001,276(32):30099-30105
CtpA, a carboxyl-terminal processing protease, is a member of a novel family of endoproteases that includes a tail-specific protease from Escherichia coli. In oxygenic photosynthetic organisms, CtpA catalyzes C-terminal processing of the D1 protein of photosystem II, an essential event for the assembly of a manganese cluster and consequent light-mediated water oxidation. We introduced site-specific mutations at 14 conserved residues of CtpA in the cyanobacterium Synechocystis sp. PCC 6803 to examine their functional roles. Analysis of the photoautotrophic growth capabilities of these mutants, their ability to process precursor D1 protein and hence evolve oxygen, along with an estimation of the protease content in the mutants revealed that five of these residues are critical for in vivo activity of CtpA. Recent x-ray crystal structure analysis of CtpA from the eukaryotic alga Scenedesmus obliquus (Liao, D.-I., Qian, J., Chisholm, D. A., Jordan, D. B. and Diner, B. A. (2000) Nat. Struct. Biol. 7, 749-753) has shown that the residues equivalent to Ser-313 and Lys-338, two of the five residues mentioned above, form the catalytic center of this enzyme. Our in vivo analysis demonstrates that the three other residues, Asp-253, Arg-255, and Glu-316, are also important determinants of the catalytic activity of CtpA. 相似文献
994.
Odan M Ishizuka N Hiramatsu Y Inagaki M Hashizume H Fujii Y Mitsumori S Morioka Y Soga M Deguchi M Yasui K Arimura A 《Bioorganic & medicinal chemistry letters》2012,22(8):2803-2806
The discovery of novel CB2 ligands based on the 3-carbamoyl-2-pyridone derivatives by adjusting the size of side chain at 1-, 5- and 6-position is reported. The structure-activity relationship around this template lead to the identification of S-777469 as a selective CB2 receptor agonist, which exhibited the significant inhibition of scratching induced by Compound 48/80 at 1.0 mg/kg po and 10 mg/kg po (55% and 61%, respectively). 相似文献
995.
T Hayashi M Senda H Morohashi H Higashi M Horio Y Kashiba L Nagase D Sasaya T Shimizu N Venugopalan H Kumeta NN Noda F Inagaki T Senda M Hatakeyama 《Cell host & microbe》2012,12(1):20-33
The Helicobacter pylori type IV secretion effector CagA is a major bacterial virulence determinant and critical for gastric carcinogenesis. Upon delivery into gastric epithelial cells, CagA localizes to the inner face of the plasma membrane, where it acts as a pathogenic scaffold/hub that promiscuously recruits host proteins to potentiate oncogenic signaling. We find that CagA comprises a structured N-terminal region and an intrinsically disordered C-terminal region that directs versatile protein interactions. X-ray crystallographic analysis of the N-terminal CagA fragment (residues 1-876) revealed that the region has a structure comprised of three discrete domains. Domain I constitutes a mobile CagA N terminus, while Domain II tethers CagA to the plasma membrane by interacting with membrane phosphatidylserine. Domain III interacts intramolecularly with the intrinsically disordered C-terminal region, and this interaction potentiates the pathogenic scaffold/hub function of CagA. The present work provides a tertiary-structural basis for the pathophysiological/oncogenic action of H. pylori CagA. 相似文献
996.
997.
The Fox-1 family and SUP-12 coordinately regulate tissue-specific alternative splicing in vivo 总被引:2,自引:0,他引:2 下载免费PDF全文
Many pre-mRNAs are alternatively spliced in a tissue-specific manner in multicellular organisms. The Fox-1 family of RNA-binding proteins regulate alternative splicing by either activating or repressing exon inclusion through specific binding to UGCAUG stretches. However, the precise cellular contexts that determine the action of the Fox-1 family in vivo remain to be elucidated. We have recently demonstrated that ASD-1 and FOX-1, members of the Fox-1 family in Caenorhabditis elegans, regulate tissue-specific alternative splicing of the fibroblast growth factor receptor gene, egl-15, which eventually determines the ligand specificity of the receptor in vivo. Here we report that another RNA-binding protein, SUP-12, coregulates the egl-15 alternative splicing. By screening for mutants defective in the muscle-specific expression of our alternative splicing reporter, we identified the muscle-specific RNA-binding protein SUP-12. We identified juxtaposed conserved stretches as the cis elements responsible for the regulation. The Fox-1 family and the SUP-12 proteins form a stable complex with egl-15 RNA, depending on the cis elements. Furthermore, the asd-1; sup-12 double mutant is defective in sex myoblast migration, phenocopying the isoform-specific egl-15(5A) mutant. These results establish an in vivo model that coordination of the two families of RNA-binding proteins regulates tissue-specific alternative splicing of a specific target gene. 相似文献
998.
Makiko Tsutsumi Reiko Fujiwara Haruki Nishizawa Mayuko Ito Hiroshi Kogo Hidehito Inagaki Tamae Ohye Takema Kato Takuma Fujii Hiroki Kurahashi 《PloS one》2014,9(5)
Aneuploidy in fetal chromosomes is one of the causes of pregnancy loss and of congenital birth defects. It is known that the frequency of oocyte aneuploidy increases with the human maternal age. Recent data have highlighted the contribution of cohesin complexes in the correct segregation of meiotic chromosomes. In mammalian oocytes, cohesion is established during the fetal stages and meiosis-specific cohesin subunits are not replenished after birth, raising the possibility that the long meiotic arrest of oocytes facilitates a deterioration of cohesion that leads to age-related increases in aneuploidy. We here examined the cohesin levels in dictyate oocytes from different age groups of humans and mice by immunofluorescence analyses of ovarian sections. The meiosis-specific cohesin subunits, REC8 and SMC1B, were found to be decreased in women aged 40 and over compared with those aged around 20 years (P<0.01). Age-related decreases in meiotic cohesins were also evident in mice. Interestingly, SMC1A, the mitotic counterpart of SMC1B, was substantially detectable in human oocytes, but little expressed in mice. Further, the amount of mitotic cohesins of mice slightly increased with age. These results suggest that, mitotic and meiotic cohesins may operate in a coordinated way to maintain cohesions over a sustained period in humans and that age-related decreases in meiotic cohesin subunits impair sister chromatid cohesion leading to increased segregation errors. 相似文献
999.
Kinetics of fatty acid binding ability of glycated human serum albumin (HSA) were investigated by fluorescent displacement
technique with 1-anilino-8-naphtharene sulphonic acid (ANS method), and photometric detection of nonesterified-fatty-acid
(NEFA method). Changing of binding affinities of glycated HSA toward oleic acid, linoleic acid, lauric acid, and caproic acid,
were not observed by the ANS method. However, decreases of binding capacities after 55 days glycation were confirmed by the
NEFA method in comparison to control HSA. The decrease in binding affinities was: oleic acid (84%), linoleic acid (84%), lauric
acid (87%), and caproic acid (90%), respectively. The decreases were consistent with decrease of the intact lysine residues
in glycated HSA. The present observation indicates that HSA promptly loses its binding ability to fatty acid as soon as the
lysine residues at fatty acid binding sites are glycated. 相似文献
1000.
S Suzuki J-I Mori M Kobayashi T Inagaki A Komatsu K Yamashita T Takeda T Miyamoto K Ichikawa K Hashizume 《Hormones et métabolisme》2003,35(10):577-582
Functional domains required for NADPH-binding, T(3)-binding, protein dimerization and cytosolic retention were analyzed in NADPH-dependent cytosolic 3,5,3'-triiodothyronine (T(3))-binding protein (p38CTBP) by using the deletion mutants. Wild-type p38CTBP (amino acids; 1-314) and a series of deletion mutants (amino acids; 1-79, 1-128, 1-146, 1-216, 37-314, and 1-145 with 270-314) were bacterially induced. NADPH-dependent T(3)-binding activity was not observed in all mutant p38CTBPs studied, although wild-type p38CTBP showed high-affinity T(3)-binding activity. Wild-type p38CTBP was able to bind a CL-6B column, none of the mutant p38CTBPs showed any binding activity. Pull-down analyses demonstrated that two regions between amino acid 128 and 146, and between 216 and 270, both of which possess helical structures, were required for homodimeric p38CTBP binding. In fluoroscopic studies, GFP-tagged p38CTBP was preferentially observed in cytoplasm. However, C-terminal region-deleted p38CTBP(1-216) was not only observed in cytoplasm, but also in nucleus. These results suggest that 1) multiple regions in p38CTBP molecule are required for T(3)-binding and NADPH binding, 2) two helical structures in p38CTBP molecule may be important in the homodimer formation, and 3) C-terminal region of p38CTBP contains the function to preserve the protein in cytoplasm. 相似文献