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91.
Clausen AR Matakos A Sandrini MP Piskur J 《Nucleosides, nucleotides & nucleic acids》2006,25(9-11):1159-1163
Twenty-six fully sequenced archaeal genomes were searched for genes coding for putative deoxyribonucleoside kinases (dNKs). We identified only 5 human-like thymidine kinase 1 genes (TK1s) and none for non-TK1 kinases. Four TK1s were identified in the Euryarchaea and one was found in the Crenarchaea, while none was found in Nanoarchaeum. The identified TK1s have high identity to Gram-positive bacteria TK1s. The TK1s from archaea, Gram-positive bacteria and eukaryotes share the same common ancestor, while the TK1s from Gram-negative bacteria belong to a less-related subgroup. It seems that a functional deoxyribonucleoside salvage pathway is not crucial for the archaeal cell. 相似文献
92.
Sandrini MP Clausen AR Munch-Petersen B Piskur J 《Nucleosides, nucleotides & nucleic acids》2006,25(9-11):1153-1158
Thymidine kinases (TKs) appear to be almost ubiquitous and are found in nearly all prokaryotes, eukaryotes, and several viruses. They are the key enzymes in thymidine salvage and activation of several anti-cancer and antiviral drugs. We show that bacterial TKs can be subdivided into 2 groups. The TKs from Gram-positive bacteria are more closely related to the eukaryotic TK1 enzymes than are TKs from Gram-negative bacteria. 相似文献
93.
Katrine T.-B.G. Schjoldager Henrik Clausen 《Biochimica et Biophysica Acta (BBA)/General Subjects》2012
Background
Posttranslational modifications (PTMs) greatly expand the function and regulation of proteins, and glycosylation is the most abundant and diverse PTM. Of the many different types of protein glycosylation, one is quite unique; GalNAc-type (or mucin-type) O-glycosylation, where biosynthesis is initiated in the Golgi by up to twenty distinct UDP-N-acetyl-α-d-galactosamine:polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts). These GalNAc-Ts are differentially expressed in cells and have different (although partly overlapping) substrate specificities, which provide for both unique functions and considerable redundancy. Recently we have begun to uncover human diseases associated with deficiencies in GalNAc-T genes (GALNTs). Thus deficiencies in individual GALNTs produce cell and protein specific effects and subtle distinct phenotypes such as hyperphosphatemia with hyperostosis (GALNT3) and dysregulated lipid metabolism (GALNT2). These phenotypes appear to be caused by deficient site-specific O-glycosylation that co-regulates proprotein convertase (PC) processing of FGF23 and ANGPTL3, respectively.Scope of review
Here we summarize recent progress in uncovering the interplay between human O-glycosylation and protease regulated processing and describes other important functions of site-specific O-glycosylation in health and disease.Major conclusions
Site-specific O-glycosylation modifies pro-protein processing and other proteolytic events such as ADAM processing and thus emerges as an important co-regulator of limited proteolytic processing events.General significance
Our appreciation of this function may have been hampered by our sparse knowledge of the O-glycoproteome and in particular sites of O-glycosylation. New strategies for identification of O-glycoproteins have emerged and recently the concept of SimpleCells, i.e. human cell lines made deficient in O-glycan extension by zinc finger nuclease gene targeting, was introduced for broad O-glycoproteome analysis. 相似文献94.
Henriette L. Pedersen Jonatan U. Fangel Barry McCleary Christian Ruzanski Maja G. Rydahl Marie-Christine Ralet Vladimir Farkas Laura von Schantz Susan E. Marcus Mathias C. F. Andersen Rob Field Mats Ohlin J. Paul Knox Mads H. Clausen William G. T. Willats 《The Journal of biological chemistry》2012,287(47):39429-39438
Microarrays are powerful tools for high throughput analysis, and hundreds or thousands of molecular interactions can be assessed simultaneously using very small amounts of analytes. Nucleotide microarrays are well established in plant research, but carbohydrate microarrays are much less established, and one reason for this is a lack of suitable glycans with which to populate arrays. Polysaccharide microarrays are relatively easy to produce because of the ease of immobilizing large polymers noncovalently onto a variety of microarray surfaces, but they lack analytical resolution because polysaccharides often contain multiple distinct carbohydrate substructures. Microarrays of defined oligosaccharides potentially overcome this problem but are harder to produce because oligosaccharides usually require coupling prior to immobilization. We have assembled a library of well characterized plant oligosaccharides produced either by partial hydrolysis from polysaccharides or by de novo chemical synthesis. Once coupled to protein, these neoglycoconjugates are versatile reagents that can be printed as microarrays onto a variety of slide types and membranes. We show that these microarrays are suitable for the high throughput characterization of the recognition capabilities of monoclonal antibodies, carbohydrate-binding modules, and other oligosaccharide-binding proteins of biological significance and also that they have potential for the characterization of carbohydrate-active enzymes. 相似文献
95.
96.
David Spooner Shelley Jansky Andrea Clausen Maria del Rosario Herrera Marc Ghislain 《Economic botany》2012,66(1):12-21
The Enigma of
Solanum maglia
in the Origin of the Chilean Cultivated Potato,
Solanum tuberosum
Chilotanum Group. Landrace potato cultivars occur in two broad geographic regions: the high Andes from western Venezuela south to northern
Argentina (Solanum tuberosum Andigenum Group, “Andigenum”), and lowland south-central Chile (S. tuberosum Chilotanum Group, “Chilotanum”), with a coastal desert and 560 km between southernmost populations of Andigenum and Chilotanum.
Unlike Andigenum landraces, Chilotanum landraces are adapted to long days and carry a 241 base pair plastid DNA deletion.
However, Andigenum and Chilotanum landraces are morphologically similar. We investigated a hypothesis that Chilotanum landraces
arose from Solanum maglia, a rare tuber-bearing species found in Chile and Argentina. This hypothesis was formulated first based on morphological analyses
of starch grains of extant and preserved (12,500 years before present) S. maglia, and on putative sympatry of extant S. maglia and Chilotanum landraces. Our new starch grain analyses fail to support this hypothesis; we could find no evidence of current
sympatric distributions, and S. maglia lacks the 241-bp plastid deletion. However, microsatellite data group all accessions of S. maglia exclusively with Chilotanum, which is supported by our previous observation at the single locus of the waxy gene. These results
could be interpreted in various ways, but all explanations have problems. One explanation is that S. maglia is a progenitor of Chilotanum. However, the plastid deletion in Chilotanum but not S. maglia cannot be easily explained. Another explanation is that Chilotanum was formed by hybridization between S. maglia and pre-Chilotanum, but this conflicts with prior cladistic analyses. These new data shed light on aspects of this question
and highlight various evolutionary scenarios, but the origin of Chilotanum and the involvement of S. maglia in its origin remain an enigma. 相似文献
97.
Tennstaedt A Pöpsel S Truebestein L Hauske P Brockmann A Schmidt N Irle I Sacca B Niemeyer CM Brandt R Ksiezak-Reding H Tirniceriu AL Egensperger R Baldi A Dehmelt L Kaiser M Huber R Clausen T Ehrmann M 《The Journal of biological chemistry》2012,287(25):20931-20941
Protective proteases are key elements of protein quality control pathways that are up-regulated, for example, under various protein folding stresses. These proteases are employed to prevent the accumulation and aggregation of misfolded proteins that can impose severe damage to cells. The high temperature requirement A (HtrA) family of serine proteases has evolved to perform important aspects of ATP-independent protein quality control. So far, however, no HtrA protease is known that degrades protein aggregates. We show here that human HTRA1 degrades aggregated and fibrillar tau, a protein that is critically involved in various neurological disorders. Neuronal cells and patient brains accumulate less tau, neurofibrillary tangles, and neuritic plaques, respectively, when HTRA1 is expressed at elevated levels. Furthermore, HTRA1 mRNA and HTRA1 activity are up-regulated in response to elevated tau concentrations. These data suggest that HTRA1 is performing regulated proteolysis during protein quality control, the implications of which are discussed. 相似文献
98.
Yang Z Drew DP Jørgensen B Mandel U Bach SS Ulvskov P Levery SB Bennett EP Clausen H Petersen BL 《The Journal of biological chemistry》2012,287(15):11911-11923
Mucin-type O-glycosylation is an important post-translational modification that confers a variety of biological properties and functions to proteins. This post-translational modification has a particularly complex and differentially regulated biosynthesis rendering prediction and control of where O-glycans are attached to proteins, and which structures are formed, difficult. Because plants are devoid of GalNAc-type O-glycosylation, we have assessed requirements for establishing human GalNAc O-glycosylation de novo in plants with the aim of developing cell systems with custom-designed O-glycosylation capacity. Transient expression of a Pseudomonas aeruginosa Glc(NAc) C4-epimerase and a human polypeptide GalNAc-transferase in leaves of Nicotiana benthamiana resulted in GalNAc O-glycosylation of co-expressed human O-glycoprotein substrates. A chimeric YFP construct containing a 3.5 tandem repeat sequence of MUC1 was glycosylated with up to three and five GalNAc residues when co-expressed with GalNAc-T2 and a combination of GalNAc-T2 and GalNAc-T4, respectively, as determined by mass spectrometry. O-Glycosylation was furthermore demonstrated on a tandem repeat of MUC16 and interferon α2b. In plants, prolines in certain classes of proteins are hydroxylated and further substituted with plant-specific O-glycosylation; unsubstituted hydroxyprolines were identified in our MUC1 construct. In summary, this study demonstrates that mammalian type O-glycosylation can be established in plants and that plants may serve as a host cell for production of recombinant O-glycoproteins with custom-designed O-glycosylation. The observed hydroxyproline modifications, however, call for additional future engineering efforts. 相似文献
99.
Cancer Associated Aberrant Protein O-Glycosylation Can Modify Antigen Processing and Immune Response
Caroline B. Madsen Cecilie Petersen Kirstine Lavrsen Mikkel Harndahl S?ren Buus Henrik Clausen Anders E. Pedersen Hans H. Wandall 《PloS one》2012,7(11)
Aberrant glycosylation of mucins and other extracellular proteins is an important event in carcinogenesis and the resulting cancer associated glycans have been suggested as targets in cancer immunotherapy. We assessed the role of O-linked GalNAc glycosylation on antigen uptake, processing, and presentation on MHC class I and II molecules. The effect of GalNAc O-glycosylation was monitored with a model system based on ovalbumin (OVA)-MUC1 fusion peptides (+/− glycosylation) loaded onto dendritic cells co-cultured with IL-2 secreting OVA peptide-specific T cell hybridomas. To evaluate the in vivo response to a cancer related tumor antigen, Balb/c or B6.Cg(CB)-Tg(HLA-A/H2-D)2Enge/J (HLA-A2 transgenic) mice were immunized with a non-glycosylated or GalNAc-glycosylated MUC1 derived peptide followed by comparison of T cell proliferation, IFN-γ release, and antibody induction. GalNAc-glycosylation promoted presentation of OVA-MUC1 fusion peptides by MHC class II molecules and the MUC1 antigen elicited specific Ab production and T cell proliferation in both Balb/c and HLA-A2 transgenic mice. In contrast, GalNAc-glycosylation inhibited the presentation of OVA-MUC1 fusion peptides by MHC class I and abolished MUC1 specific CD8+ T cell responses in HLA-A2 transgenic mice. GalNAc glycosylation of MUC1 antigen therefore facilitates uptake, MHC class II presentation, and antibody response but might block the antigen presentation to CD8+ T cells. 相似文献
100.
Williams JS Clausen AR Nick McElhinny SA Watts BE Johansson E Kunkel TA 《DNA Repair》2012,11(8):649-656
We have investigated the ability of the 3′ exonuclease activity of Saccharomyces cerevisiae DNA polymerase ? (Pol ?) to proofread newly inserted ribonucleotides (rNMPs). During DNA synthesis in vitro, Pol ? proofreads ribonucleotides with apparent efficiencies that vary from none at some locations to more than 90% at others, with rA and rU being more efficiently proofread than rC and rG. Previous studies show that failure to repair ribonucleotides in the genome of rnh201Δ strains that lack RNase H2 activity elevates the rate of short deletions in tandem repeat sequences. Here we show that this rate is increased by 2–4-fold in pol2-4 rnh201Δ strains that are also defective in Pol ? proofreading. In comparison, defective proofreading in these same strains increases the rate of base substitutions by more than 100-fold. Collectively, the results indicate that although proofreading of an ‘incorrect’ sugar is less efficient than is proofreading of an incorrect base, Pol ? does proofread newly inserted rNMPs to enhance genome stability. 相似文献