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991.
Gastrointestinal tumorigenesis in Smad4 (Dpc4) mutant mice 总被引:3,自引:0,他引:3
The SMAD4 (Dpc4) gene plays a key role in the TGF-beta signaling pathway. We recently inactivated the mouse homolog Smad4. The homozygous mutants were embryonic lethals, whereas the heterozygotes were viable and fertile. Although young heterozygotes were normal, old mice developed gastric and duodenal polyps similar to those found in human juvenile polyps characterized by abundant stroma and eosinophilic infiltrations. These data are consistent with the reports that a subset of human juvenile polyposis kindreds carry germline mutations in the SMAD4 gene. We then introduced the Smad4 mutation into the Apc delta 716 knockout mice, a model for human familial adenomatous polyposis. Because both Apc and Smad4 are located on mouse chromosome 18, we constructed by meiotic recombination, compound heterozygotes carrying both mutations on the same chromosome. In such mice, intestinal polyps developed into more malignant tumors than those in the simple Apc delta 716 heterozygotes, showing an extensive stromal cell proliferation and strong submucosal invasion. These results indicate that mutations in SMAD4 play a significant role in the malignant progression of colorectal tumors. 相似文献
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994.
Wataru Otsu Takao Kurooka Yayoi Otsuka Kota Sato Mutsumi Inaba 《The Journal of biological chemistry》2013,288(25):18521-18532
Protein export from the endoplasmic reticulum (ER) depends on the interaction between a signal motif on the cargo and a cargo recognition site on the coatomer protein complex II. A hydrophobic sequence in the N terminus of the bovine anion exchanger 1 (AE1) anion exchanger facilitated the ER export of human AE1Δ11, an ER-retained AE1 mutant, through interaction with a specific Sec24 isoform. The cell surface expression and N-glycan processing of various substitution mutants or chimeras of human and bovine AE1 proteins and their Δ11 mutants in HEK293 cells were examined. The N-terminal sequence (V/L/F)X(I/L)X(M/L), 26VSIPM30 in bovine AE1, which is comparable with ΦXΦXΦ, acted as the ER export signal for AE1 and AE1Δ11 (Φ is a hydrophobic amino acid, and X is any amino acid). The AE1-Ly49E chimeric protein possessing the ΦXΦXΦ motif exhibited effective cell surface expression and N-glycan maturation via the coatomer protein complex II pathway, whereas a chimera lacking this motif was retained in the ER. A synthetic polypeptide containing the N terminus of bovine AE1 bound the Sec23A-Sec24C complex through a selective interaction with Sec24C. Co-transfection of Sec24C-AAA, in which the residues 895LIL897 (the binding site for another ER export signal motif IXM on Sec24C and Sec24D) were mutated to 895AAA897, specifically increased ER retention of the AE1-Ly49E chimera. These findings demonstrate that the ΦXΦXΦ sequence functions as a novel signal motif for the ER export of cargo proteins through an exclusive interaction with Sec24C. 相似文献
995.
Two apyrases having different substrate specificity, MP67 and MpAPY2, are present in Mimosa pudica. The substrate specificity of MP67 is quite high against ADP, and is distinct from any other apyrase. This might be attributed to the nucleotide binding motif (DXG) in apyrase conserved region 1. We performed a single amino acid substitution at position X in the motif. The ratio of the velocity of ATP/ADP hydrolysis was higher (approximately 1) for the S63A-MP67 mutant than for wild type-MP67 (0.19). Binding affinity for ADP of A75S-MpAPY2 mutant was increased to a level higher than that of the wild type MpAPY2. Thus, the residue at position X in the DXG motif plays an important role in determining nucleotide preference. 相似文献
996.
Adulsak Wijit Atiporn Saeung Visut Baimai Yasushi Otsuka Sorawat Thongsahuan Kritsana Taai Wichai Srisuka Siripan Songsawatkiat Sriwatapron Sor-suwan Chayanit Hempolchom Pradya Somboon Wej Choochote 《Comptes rendus biologies》2013,336(9):449-456
Eight species members of the Thai Hyrcanus Group were identified based on the intact morphology and molecular analysis (COI barcoding, 658 bp) of F1-progenies. Five iso-female lines of each species were pooled in order to establish stock colonies. A stenogamous colony of each species was investigated by making 200 and 300 newly emerged adult females and males co-habit in a 30 cm cubic cage for one week. After ovipositon, the spermathecae of females were examined for sperms. The results revealed that Anopheles argyropus, Anopheles crawfordi, Anopheles nitidus, Anopheles pursati, Anopheles sinensis, Anopheles nigerrimus, Anopheles paraliae and Anopheles peditaeniatus yielded insemination rates of 0%, 0%, 0%, 31%, 33%, 42%, 50% and 77%, respectively. Continuous selection to establish stenogamous colonies indicated that An. sinensis, An. pursati, An. nigerrimus, An. paraliae and An. peditaeniatus provided insemination rates of 33–34%, 27–31%, 42–58%, 43–57% and 61–86% in 1, 2, 5, 6 and 20 generations of passages, respectively. 相似文献
997.
Kiyoshi Yoshizawa Masamitsu Itoh Kazuhide Aida Ken-ichi Otsuka 《Bioscience, biotechnology, and biochemistry》2013,77(8):1262-1264
Partially purified lipoxygenase (LOX) extracts were obtained from Fusarium proliferatum, Fusarium oxysporum, Chlorella pyrenoidosa, and Saccharomyces cerevisiae; the enzymatic extract of F. proliferatum showed the highest LOX activity while those of F. oxysporum and S. cerevisiae demonstrated only 27.8 and 16.5% of the activity at pH 8.0, and 61.2 and 9.7% of the enzyme activity at pH 10.0, respectively. The lowest LOX activity was that in the C. pyrenoidosa extract. The microbial enzymatic preparations were assayed with linoleic acid as substrate, which was bioconverted into 9- and 13-hydroperoxides (HPODEs) by all four extracts; in additon, the LOX activity in the F. oxysporum extract produced the 10- and 12-HPODEs from linoleic acid while that of the C. pyrenoidosa extract produced only the 10- HPODE. When assayed with the 9- and 13-HPODEs as substrates, the selected microbial extracts had secondary enzyme activities, one of which produced hexanal. The highest hexanal-producing activity was 1.51 and 1.39 nmol hexanol/mg protein/min in the F. proliferatum and C. pyrenoidosa extracts, respectively, while those of F. oxysporum and S. cerevisiae had approximately 15% of the HPODE-cleaving enzyme activity. The C. pyrenoidosa extract had the highest proportion of pentanone, which was produced at only one-fourth the concentration by the HPODE-cleaving enzyme activity in the three other microbial enzymatic extracts. 相似文献
998.
Ken-ichi Otsuka Masamitsu Itoh Kiyoshi Yoshizawa 《Bioscience, biotechnology, and biochemistry》2013,77(5):1013-1017
In this paper a new method of chemical determination of mevalonic acid in fermented materials is described. Mevalonic acid is identified as hydroxamate of its lactone using thin-layer chromatography, and is determined quantitatively as lactone-form by gas liquid chromatography. Mevalonic acid separated from kôji extract was identified by analysis of infrared spectrum. Saké and Kôji contained 4.6 μ/ml and 43.3 μ/g of this acid, respectively. 相似文献
999.
Siolipin has shown three biological activities; (1) hemolytic action for rabbit erythrocyte, (2) acceleration of fibrin clot formation, (3) antibacterial activity on Bacillus subtilis PCI-219 grown on a synthetic medium (1% glucose, 01% KH2PO4, 0.1% (NH4)2HPO4, 0.5% NaCl, 0.04% MgSO4·7H2O, 1.5% agar). The antibacterial activity of siolipin was reversed by l-histidine, l-cysteine etc. 相似文献
1000.
Takayuki Shiroyama Norio Okamoto Hidekazu Suzuki Motohiro Tamiya Tadahiro Yamadori Naoko Morishita Tomoyuki Otsuka Satomu Morita Kanako Kurata Akira Okimura Kunimitsu Kawahara Shinji Sasada Tomonori Hirashima Ichiro Kawase 《PloS one》2013,8(12)