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731.
He H Dang Y Dai F Guo Z Wu J She X Pei Y Chen Y Ling W Wu C Zhao S Liu JO Yu L 《The Journal of biological chemistry》2003,278(31):29278-29287
The molecular machinery required for autophagy is highly conserved in all eukaryotes as seen by the high degree of conservation of proteins involved in the formation of the autophagosome membranes. Recently, both yeast Apg8p and its rat homologue Map1lc3 were identified as essential constituents of autophagosome membrane as a processed form. In addition, both the yeast and human proteins exist in two modified forms produced by a series of post-translational modifications including a critical C-terminal cleavage after a conserved Gly residue, and the smaller processed form is associated with the autophagosome membranes. Herein, we report the identification and characterization of three human orthologs of the rat Map1LC3, named MAP1LC3A, MAP1LC3B, and MAP1LC3C. We show that the three isoforms of human MAP1LC3 exhibit distinct expression patterns in different human tissues. Importantly, we found that the three isoforms of MAP1LC3 differ in their post-translation modifications. Although MAP1LC3A and MAP1LC3C are produced by the proteolytic cleavage after the conserved C-terminal Gly residue, like their rat counterpart, MAP1LC3B does not undergo C-terminal cleavage and exists in a single modified form. The essential site for the distinct post-translation modification of MAP1LC3B is Lys-122 rather than the conserved Gly-120. Subcellular localization by cell fractionation and immunofluorescence revealed that three human isoforms are associated with membranes involved in the autophagic pathway. These results revealed different regulation of the three human isoforms of MAP1LC3 and implicate that the three isoforms may have different physiological functions. 相似文献
732.
The incidence of type 1 diabetes is increasing worldwide and the disease is an onerous burden both to the individual and to society. There are thus important reasons to screen for the disease before it becomes manifest: (1) to improve understanding of the natural history of the prediabetic period; (2) to gain further insights into the immunopathogenesis of the disease; (3) to identify individuals for prevention trials; (4) to make an earlier diagnosis in order to reduce morbidity and mortality. Great strides have been made, yet there is still a great deal to be learned. Opponents of screening argue that screening tests for the disease have a low positive predictive value and that predicting the disease without a primary prevention capability raises ethical considerations because of induced stress, lifestyle changes, cost and potential effects on insurability. The greatest single barrier against large-scale population screening and prevention of the disease remains the lack of an effective intervention. However, screening in the context of well-designed research studies must continue - ultimately the benefit to the individual and to society will be immense. 相似文献
733.
Rapid identification of probiotic lactobacillus biosurfactant proteins by ProteinChip tandem mass spectrometry tryptic peptide sequencing 总被引:2,自引:0,他引:2
Reid G Gan BS She YM Ens W Weinberger S Howard JC 《Applied and environmental microbiology》2002,68(2):977-980
A novel ProteinChip-interfaced tandem mass spectrometer was employed to identify collagen binding proteins from biosurfactant produced by Lactobacillus fermentum RC-14. On-chip tryptic digestion of the captured collagen binding proteins resulted in rapid sequence identification of five novel tryptic peptide sequences via collision-induced dissociation tandem mass spectrometry. 相似文献
734.
Fu LH Wang XF Eyal Y She YM Donald LJ Standing KG Ben-Hayyim G 《The Journal of biological chemistry》2002,277(29):25983-25991
Selenoproteins that contain the rare amino acid selenocysteine in their primary structure have been identified in diverse organisms such as viruses, bacteria, archea, and mammals, but so far not in yeast or plants. Among the most thoroughly investigated families of selenoenzymes are the animal glutathione peroxidases (GPXs). In the last few years, genes encoding GPX-like homologues from Chlamydomonas and higher plants have been isolated, but, unlike the animal ones, all of them have cysteine (rather than selenocysteine) residues in their catalytic site. In all organisms investigated that contain selenoproteins, selenocysteine is encoded by a UGA opal codon, which is usually a stop codon. We report here that, in Chlamydomonas reinhardtii, the cDNA-cloned sequence of a GPX homologue contains an internal TGA codon in frame to the ATG. Specific mRNA expression, protein production, and enzyme activity are selenium-dependent. Sequence analysis of the peptides produced by proteolytic digestion, performed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), confirmed the presence of a selenocysteine residue at the predicted site and suggest its location in the mitochondria. Thus, our data present the first direct proof that a UGA opal codon is decoded in the plant kingdom to incorporate selenocysteine. 相似文献
735.
Zhang S Cai M Zhang S Xu S Chen S Chen X Chen C Gu J 《The Journal of biological chemistry》2002,277(38):35314-35322
The p58(PITSLRE) is a p34(cdc2)-related protein kinase that plays an important role in normal cell cycle progression. Elevated expression of p58(PITSLRE) in eukaryotic cells prevents them from undergoing normal cytokinesis and appears to delay them in late telophase. To investigate the molecular mechanism of p58(PITSLRE) action, we used the yeast two-hybrid system, screened a human fetal liver cDNA library, and identified cyclin D3 as an interacting partner of p58(PITSLRE). In vitro binding assay, in vivo coimmunoprecipitation, and immunofluorescence cell staining further confirmed the association of p58(PITSLRE) with cyclin D3. This binding was observed only in the G(2)/M phase but not in the G(1)/S phase of the cell cycle; meanwhile, no interaction between p110(PITSLRE) and cyclin D3 was observed in all the cell cycle. The overexpression of cyclin D3 in 7721 cells leads to an exclusively accumulation of p58(PITSLRE) in the nuclear region, affecting its cellular distribution. Histone H1 kinase activity of p58(PITSLRE) was greatly enhanced upon interaction with cyclin D3. Furthermore, kinase activity of p58(PITSLRE) was found to increase greatly in the presence of cyclin D3 using a specific substrate, beta-1,4-galactosyltransferase 1. These data provide a new clue to our understanding of the cellular function of p58(PITSLRE) and cyclin D3. 相似文献
736.
Casp CB She JX McCormack WT 《Pigment cell research / sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society》2002,15(1):62-66
Vitiligo susceptibility is a complex genetic trait that may involve genes important for melanin biosynthesis, response to oxidative stress, and/or regulation of autoimmunity, as well as environmental factors. We report here case-control and family-based association studies for the catalase gene (CAT) in vitiligo patients. The CAT gene was selected as a candidate gene because of the reduction of catalase enzyme activity (EC 1.11.1.6) and concomitant accumulation of excess hydrogen peroxide observed in the entire epidermis of vitiligo patients. One of three CAT genetic markers studied was found to be informative for genotypic analysis of Caucasian vitiligo patients and control subjects. Both case/control and family-based genetic association studies of the T/C single nucleotide polymorphism (SNP) in exon 9 of the CAT gene, which is detectable with the restriction endonuclease BstX I, suggest possible association between the CAT gene and vitiligo susceptibility. The observations that T/C heterozygotes are more frequent among vitiligo patients than controls and that the C allele is transmitted more frequently to patients than controls suggest that linked mutations in or near the CAT gene might contribute to a quantitative deficiency of catalase activity in the epidermis and the accumulation of excess hydrogen peroxide (H2O2). The CAT gene may, therefore, be a susceptibility gene in some vitiligo patients, further supporting the epidermal oxidative stress model for vitiligo pathogenesis. 相似文献
737.
Peptidomimetics of efflux pump inhibitors potentiate the activity of levofloxacin in Pseudomonas aeruginosa 总被引:3,自引:0,他引:3
Renau TE Léger R Yen R She MW Flamme EM Sangalang J Gannon CL Chamberland S Lomovskaya O Lee VJ 《Bioorganic & medicinal chemistry letters》2002,12(5):763-766
Several classes of peptidomimetics of the efflux pump inhibitor D-ornithine-D-homophenylalanine-3-aminoquinoline (MC-02,595) have been prepared and evaluated for their ability to potentiate the activity of the fluoroquinolone levofloxacin in Pseudomonas aeruginosa. A number of the new analogues were as active or more active than the lead, demonstrating that a peptide backbone is not essential for activity. 相似文献
738.
Glycoprotein IIb/IIIa complex, a platelet surface fibrinogen receptor, plays a key role in producing primary hemostasis. At present, only a single mutation in the GPIIla gene, Leu33Pro, and a single mutation in the GPIIb gene, lle843Ser, has been described. The mutations are known to enhance signaling functions of the receptor and are associated with the development of arterial thromboses. In the present study, we describe a novel GPIIIa mutation, which is T to G nucleotide substitution in position 1585, resulting in the replacement of Leu for Arg in position 40 of the amino acid sequence of the protein. 相似文献
739.
She M Decker CJ Sundramurthy K Liu Y Chen N Parker R Song H 《Nature structural & molecular biology》2004,11(3):249-256
A major pathway of eukaryotic mRNA turnover begins with deadenylation, followed by decapping and 5'-->3' exonucleolytic degradation. A critical step in this pathway is decapping, which is carried out by an enzyme composed of Dcp1p and Dcp2p. The crystal structure of Dcp1p shows that it markedly resembles the EVH1 family of protein domains. Comparison of the proline-rich sequence (PRS)-binding sites in this family of proteins with Dcp1p indicates that it belongs to a novel class of EVH1 domains. Mapping of the sequence conservation on the molecular surface of Dcp1p reveals two prominent sites. One of these is required for the function of the Dcp1p-Dcp2p complex, and the other, corresponding to the PRS-binding site of EVH1 domains, is probably a binding site for decapping regulatory proteins. Moreover, a conserved hydrophobic patch is shown to be critical for decapping. 相似文献
740.
Lee BH Min X Heise CJ Xu BE Chen S Shu H Luby-Phelps K Goldsmith EJ Cobb MH 《Molecular cell》2004,15(5):741-751
WNK (with no lysine [K]) protein kinases were named for their unique active site organization. Mutations in WNK1 and WNK4 cause a familial form of hypertension by undefined mechanisms. Here, we report that WNK1 selectively binds to and phosphorylates synaptotagmin 2 (Syt2) within its calcium binding C2 domains. Endogenous WNK1 and Syt2 coimmunoprecipitate and colocalize on a subset of secretory granules in INS-1 cells. Phosphorylation by WNK1 increases the amount of Ca2+ required for Syt2 binding to phospholipid vesicles; mutation of threonine 202, a WNK1 phosphorylation site, partially prevents this change. These findings suggest that phosphorylation of Syts by WNK1 can regulate Ca2+ sensing and the subsequent Ca2+-dependent interactions mediated by Syt C2 domains. These findings provide a biochemical mechanism that could lead to the retention or insertion of proteins in the plasma membrane. Interruption of this regulatory pathway may disturb membrane events that regulate ion balance. 相似文献