umu.sePublications
Change search
Refine search result
1 - 24 of 24
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Blomberg, Jeanette
    et al.
    Umeå University, Faculty of Medicine, Molecular Biology (Faculty of Medicine).
    Ruuth, Kristina
    Umeå University, Faculty of Medicine, Molecular Biology (Faculty of Medicine).
    Jacobsson, Maria
    Umeå University, Faculty of Medicine, Molecular Biology (Faculty of Medicine).
    Höglund, Andreas
    Umeå University, Faculty of Science and Technology, Molecular Biology (Faculty of Science and Technology).
    Nilsson, Jonas A
    Umeå University, Faculty of Science and Technology, Molecular Biology (Faculty of Science and Technology).
    Lundgren, Erik
    Umeå University, Faculty of Medicine, Molecular Biology (Faculty of Medicine).
    Reduced FAS transcription in clones of U937 cells that have acquired resistance to Fas-induced apoptosis2009In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 276, no 2, p. 497-508Article in journal (Refereed)
    Abstract [en]

    Susceptibility to cell death is a prerequisite for the elimination of tumour cells by cytotoxic immune cells, chemotherapy or irradiation. Activation of the death receptor Fas is critical for the regulation of immune cell homeostasis and efficient killing of tumour cells by apoptosis. To define the molecular changes that occur during selection for insensitivity to Fas-induced apoptosis, a resistant variant of the U937 cell line was established. Individual resistant clones were isolated and characterized. The most frequently observed defect in the resistant cells was reduced Fas expression, which correlated with decreased FAS transcription. Clones with such reduced Fas expression also displayed partial cross-resistance to tumour necrosis factor-alpha stimulation, but the mRNA expression of tumour necrosis factor receptors was not decreased. Reintroduction of Fas conferred susceptibility to Fas but not to tumour necrosis factor-alpha stimulation, suggesting that several alterations could be present in the clones. The reduced Fas expression could not be explained by mutations in the FAS coding sequence or promoter region, or by silencing through methylations. Protein kinase B and extracellular signal-regulated kinase, components of signalling pathways downstream of Ras, were shown to be activated in some of the resistant clones, but none of the three RAS genes was mutated, and experiments using chemical inhibitors could not establish that the activation of these proteins was the cause of Fas resistance as described in other systems. Taken together, the data illustrate that Fas resistance can be caused by reduced Fas expression, which is a result of an unidentified mode of regulation.

  • 2. Carter, J.
    et al.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Hafizi, S.
    Sequence-specific epigenetic variation in the TNS3 gene promoter and its relation to Tensin3 expression in human kidney cancer2012In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 279, p. 486-486Article in journal (Other academic)
  • 3.
    Eneqvist, Therese
    et al.
    Umeå University, Faculty of Science and Technology, Umeå Centre for Molecular Pathogenesis (UCMP).
    Lundberg, Erik
    Umeå University, Faculty of Science and Technology, Umeå Centre for Molecular Pathogenesis (UCMP).
    Nilsson, Lars
    Umeå University, Faculty of Science and Technology, Umeå Centre for Molecular Pathogenesis (UCMP).
    Abagyan, Ruben
    Sauer-Eriksson, A. Elisabeth
    Umeå University, Faculty of Science and Technology, Umeå Centre for Molecular Pathogenesis (UCMP).
    The transthyretin-related protein family2003In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 270, no 3, p. 518-532Article in journal (Refereed)
    Abstract [en]

    A number of proteins related to the homotetrameric transport protein transthyretin (TTR) forms a highly conserved protein family, which we present in an integrated analysis of data from different sources combined with an initial biochemical characterization. Homologues of the transthyretin-related protein (TRP) can be found in a wide range of species including bacteria, plants and animals, whereas transthyretins have so far only been identified in vertebrates. A multiple sequence alignment of 49 TRP sequences from 47 species to TTR suggests that the tertiary and quaternary features of the three-dimensional structure are most likely preserved. Interestingly, while some of the TRP orthologues show as little as 30% identity, the residues at the putative ligand-binding site are almost entirely conserved. RT/PCR analysis in Caenorhabditis elegans confirms that one TRP gene is transcribed, spliced and predominantly expressed in the worm, which suggests that at least one of the two C. elegans TRP genes encodes a functional protein. We used double-stranded RNA-mediated interference techniques in order to determine the loss-of-function phenotype for the two TRP genes in C. elegans but detected no apparent phenotype. The cloning and initial characterization of purified TRP from Escherichia coli reveals that, while still forming a homotetramer, this protein does not recognize thyroid hormones that are the natural ligands of TTR. The ligand for TRP is not known; however, genomic data support a functional role involving purine catabolism especially linked to urate oxidase (uricase) activity.

  • 4.
    Fowler, Christopher J.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Transport of endocannabinoids across the plasma membrane and within the cell2013In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 280, no 9, p. 1895-1904Article, review/survey (Refereed)
    Abstract [en]

    Endocannabinoids are readily accumulated from the extracellular space by cells. Although their uptake properties have the appearance of a process of facilitated diffusion, it is by no means clear as to whether there is a plasma membrane transporter dedicated to this task. Intracellular carrier proteins that shuttle the endocannabinoid anandamide from the plasma membrane to its intracellular targets such as the metabolic enzyme, fatty acid amide hydrolase, have been identified. These include proteins with other primary functions, such as fatty-acid-binding proteins and heat shock protein70, and possibly a fatty acid amide hydrolase-like anandamide transporter protein. Thus, anandamide uptake can be adequately described as a diffusion process across the plasma membrane followed by intracellular carrier-mediated transport to effector molecules, catabolic enzymes and sequestration sites, although it is recognized that different cells are likely to utilize different mechanisms of endocannabinoid transport depending upon the utility of the endocannabinoid for the cell in question.

  • 5. Fraqueza, G.
    et al.
    Carvalho, L.
    Marques, P.
    Ohlin, C. Andre
    Casey, W.
    Aureliano, M.
    Functional and structural interactions of Nb, V, Mo and W oxometalates with the sarcoplasmic reticulum Ca2(+) -ATPase reveal new insights into inhibition processes: a combination of NMR, Raman, AA and EPR spectroscopie with kinetic studies2012In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 279, no 1, SIArticle in journal (Refereed)
  • 6. Fritz, Günter
    et al.
    Botelho, Hugo M
    Morozova-Roche, Ludmilla A
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Gomes, Cláudio M
    Natural and amyloid self-assembly of S100 proteins: structural basis of functional diversity2010In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 277, no 22, p. 4578-4590Article in journal (Refereed)
    Abstract [en]

    The S100 proteins are 10-12 kDa EF-hand proteins that act as central regulators in a multitude of cellular processes including cell survival, proliferation, differentiation and motility. Consequently, many S100 proteins are implicated and display marked changes in their expression levels in many types of cancer, neurodegenerative disorders, inflammatory and autoimmune diseases. The structure and function of S100 proteins are modulated by metal ions via Ca(2+) binding through EF-hand motifs and binding of Zn(2+) and Cu(2+) at additional sites, usually at the homodimer interfaces. Ca(2+) binding modulates S100 conformational opening and thus promotes and affects the interaction with p53, the receptor for advanced glycation endproducts and Toll-like receptor 4, among many others. Structural plasticity also occurs at the quaternary level, where several S100 proteins self-assemble into multiple oligomeric states, many being functionally relevant. Recently, we have found that the S100A8/A9 proteins are involved in amyloidogenic processes in corpora amylacea of prostate cancer patients, and undergo metal-mediated amyloid oligomerization and fibrillation in vitro. Here we review the unique chemical and structural properties of S100 proteins that underlie the conformational changes resulting in their oligomerization upon metal ion binding and ultimately in functional control. The possibility that S100 proteins have intrinsic amyloid-forming capacity is also addressed, as well as the hypothesis that amyloid self-assemblies may, under particular physiological conditions, affect the S100 functions within the cellular milieu.

  • 7. Guerra, Lina
    et al.
    Guidi, Riccardo
    Frisan, Teresa
    Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
    Do bacterial genotoxins contribute to chronic inflammation, genomic instability and tumor progression?2011In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 278, no 23, p. 4577-4588Article, review/survey (Refereed)
    Abstract [en]

    Cytolethal distending toxin, produced by several Gram-negative bacteria, and colibactin, secreted by several commensal and extraintestinal pathogenic Escherichia coli strains, are the first bacterial genotoxins to be described to date. Exposure to cytolethal distending toxin and colibactin induces DNA damage, and consequently activates the DNA damage response, resulting in cell cycle arrest of the intoxicated cells and DNA repair. Irreversible DNA damage will lead to cell death by apoptosis or to senescence. It is well established that chronic exposure to DNA damaging agents, either endogenous (reactive oxygen species) or exogenous (ionizing radiation), may cause genomic instability as a result of the alteration of genes coordinating the DNA damage response, thus favoring tumor initiation and progression. In this review, we summarize the state of the art of the biology of cytolethal distending toxin and colibactin, focusing on the activation of the DNA damage response and repair pathways, and discuss the cellular responses induced in intoxicated cells, as well as how prolonged intoxication may lead to chronic inflammation, the accumulation of genomic instability, and tumor progression in both in vitro and in vivo models.

  • 8.
    Hauser, Jannek
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Grundström, Christine
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Kumar, Ramesh
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Grundström, Thomas
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Signal regulated localisation of a mutagenic protein complex at the Igh locus2015In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 282, p. 13-13Article in journal (Other academic)
    Abstract [en]

    Our system to produce antibodies is critical for our survival against numerous infections, but it causes also many tumors. B-lymphocytes can modify their immunoglobulin (Ig) genes to generate specific antibodies with a new isotype and enhanced affinity against an antigen. Activation-induced cytidine deaminase (AID) is the key mutagenic enzyme that initiates these processes by deaminating cytosine to uracil. How somatic hypermutation (SH) and class switch recombination (CSR) are targeted is key to understanding the defect DNA integrity in lymphomas and also in other tumors where inflammatory signals aberrantly induces AID. The trans-acting factors mediating specific targeting of AID and thereby SH and CSR have remained elusive. Here we show that mutant E2A with defect inhibition by the Ca2+sensor protein calmodulin results in reduced B cell receptor- (BCR-), IL4-plus CD40 ligand-stimulated CSR to IgE and instead aberrant CSR. AID is shown to be together with the transcription factors E2A, PAX5 and IRF4 in a complex on key sequences of the Igh locus in activated mouse splenic B cells. Calmodulin shows proximity with each of them after BCR stimulation. Direct protein-protein interactions enable formation of the complexes. BCR signaling reduces binding of the proteins to some of the target sites on the Igh locus, and calmodulin resistance of E2A blocks reduction of binding to these target sites and increases binding to other target sites. Thus, E2A, AID, PAX5 and IRF4 are components of a CSR and SH complex that is redistributed on the IgH gene by BCR signaling through calmodulin binding.

  • 9. Heller, K
    et al.
    Ochtrop, Philipp
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Albers, Michael
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Hedberg, Christian
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Itzen, A
    Enzymatic phosphocholination as a tool for protein labeling2015In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 282, p. 12-12Article in journal (Other academic)
    Abstract [en]

    Posttranslational modification (PTM) of proteins is a versatile cellular process to regulate the activities of proteins. The high regioselectivity and catalysis rate of posttranslationally modifying enzymes utilizing high-energy precursors can potentially be exploited to equip proteins or peptide sequences with a label of choice site selectively and efficiently. We and others have recently described and analyzed a new reversible PTM called phosphocholination in which a phosphocholine group is transferred from a cytidine diphosphate choline (CDP-choline) to a serine residue of the small GTPase Rab1 [1–3]. The enzymes AnkX and Lem3 catalyze the modification and the corresponding demodification reactions, respectively. Interestingly, we could demonstrate that the modifying enzyme AnkX only requires a short amino acid sequence for substrate recognition. Therefore, we envision AnkX as a tool for the site directed labeling of target proteins. Here we report on the progress of developing a novel reversible protein labeling strategy based on the enzymes AnkX and Lem3 and on derivatives of CDP-choline. We demonstrate the optimization of AnkX and Lem3 enzyme activities and the identification of optimal and minimal peptide target sequences. Results indicate that indeed arbitrary proteins of interest can be functionalized with phosphocholine derivatives. In summary, this work yields first insights into the development of a CDP-choline based fully reversible protein labeling strategy.

  • 10. Klinger, Stine C.
    et al.
    Højland, Anne
    Jain, Shweta
    Kjolby, Mads
    Madsen, Peder
    Svendsen, Anna Dorst
    Olivecrona, Gunilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Bonifacino, Juan S.
    Nielsen, Morten S.
    Polarized trafficking of the sorting receptor SorLA in neurons and MDCK cells2016In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 283, no 13, p. 2476-2493Article in journal (Refereed)
    Abstract [en]

    The sorting receptor SorLA is highly expressed in neurons and is also found in other polarized cells. The receptor has been reported to participate in the trafficking of several ligands, some of which are linked to human diseases, including the amyloid precursor protein, TrkB, and Lipoprotein Lipase (LpL). Despite this, only the trafficking in nonpolarized cells has been described so far. Due to the many differences between polarized and nonpolarized cells, we examined the localization and trafficking of SorLA in epithelial Madin-Darby canine kidney (MDCK) cells and rat hippocampal neurons. We show that SorLA is mainly found in sorting endosomes and on the basolateral surface of MDCK cells and in the somatodendritic domain of neurons. This polarized distribution of SorLA respectively depends on an acidic cluster and an extended version of this cluster and involves the cellular adaptor complex AP-1. Furthermore, we show that SorLA can mediate transcytosis across a tight cell layer.

  • 11.
    Lundberg, Erik
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Olofsson, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Westermark, Gunilla T
    Sauer-Eriksson, A Elisabeth
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Stability and fibril formation properties of human and fish transthyretin, and of the Escherichia coli transthyretin-related protein2009In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 276, no 7, p. 1999-2011Article in journal (Refereed)
    Abstract [en]

    Human transthyretin (hTTR) is one of several proteins known to cause amyloid disease. Conformational changes in its native structure result in aggregation of the protein, leading to insoluble amyloid fibrils. The transthyretin (TTR)-related proteins comprise a protein family of 5-hydroxyisourate hydrolases with structural similarity to TTR. In this study, we tested the amyloidogenic properties, if any, of sea bream TTR (sbTTR) and Escherichia coli transthyretin-related protein (ecTRP), which share 52% and 30% sequence identity, respectively, with hTTR. We obtained filamentous structures from all three proteins under various conditions, but, interestingly, different structures displayed different tinctorial properties. hTTR and sbTTR formed thin, curved fibrils at low pH (pH 2-3) that bound thioflavin-T (thioflavin-T-positive) but did not stain with Congo Red (CR) (CR-negative). Aggregates formed at the slightly higher pH of 4.0-5.5 had different morphology, displaying predominantly amorphous structures. CR-positive material of hTTR was found in this material, in agreement with previous results. ecTRP remained soluble at pH 2-12 at ambient temperatures. By raising of the temperature, fibril formation could be induced at neutral pH in all three proteins. Most of these temperature-induced fibrils were thicker and straighter than the in vitro fibrils seen at low pH. In other words, the temperature-induced fibrils were more similar to fibrils seen in vivo. The melting temperature of ecTRP was 66.7 degrees C. This is approximately 30 degrees C lower than the melting temperatures of sbTTR and hTTR. Information from the crystal structures was used to identify possible explanations for the reduced thermostability of ecTRP.

  • 12.
    Morozova-Roche, Ludmilla
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Pro-inflammatory S100a9 protein involved in the amyloid-neuroinflammatory cascade in Alzheimer's disease serves as a robust biomarker differentiating early stages of dementia2017In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 284, p. 138-139Article in journal (Other academic)
  • 13.
    Morozova-Roche, Ludmilla A
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Protein misfolding and self-assembly: acquired functions and their therapeutic and pathological significance2010In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 277, no 22, p. 4577-Article in journal (Refereed)
  • 14. Mossberg, Ann-Kristin
    et al.
    Hun Mok, Kenneth
    Morozova-Roche, Ludmilla A
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Svanborg, Catharina
    Structure and function of human α-lactalbumin made lethal to tumor cells (HAMLET)-type complexes2010In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 277, no 22, p. 4614-4625Article in journal (Refereed)
    Abstract [en]

    Human α-lactalbumin made lethal to tumor cells (HAMLET) and equine lysozyme with oleic acid (ELOA) are complexes consisting of protein and fatty acid that exhibit cytotoxic activities, drastically differing from the activity of their respective proteinaceous compounds. Since the discovery of HAMLET in the 1990s, a wealth of information has been accumulated, illuminating the structural, functional and therapeutic properties of protein complexes with oleic acid, which is summarized in this review. In vitro, both HAMLET and ELOA are produced by using ion-exchange columns preconditioned with oleic acid. However, the complex of human α-lactalbumin with oleic acid with the antitumor activity of HAMLET was found to be naturally present in the acidic fraction of human milk, where it was discovered by serendipity. Structural studies have shown that α-lactalbumin in HAMLET and lysozyme in ELOA are partially unfolded, 'molten-globule'-like, thereby rendering the complexes dynamic and in conformational exchange. HAMLET exists in the monomeric form, whereas ELOA mostly exists as oligomers and the fatty acid stoichiometry varies, with HAMLET holding an average of approximately five oleic acid molecules, whereas ELOA contains a considerably larger number (11- 48). Potent tumoricidal activity is found in both HAMLET and ELOA, and HAMLET has also shown strong potential as an antitumor drug in different in vivo animal models and clinical studies. The gain of new, beneficial function upon partial protein unfolding and fatty acid binding is a remarkable phenomenon, and may reflect a significant generic route of functional diversification of proteins via varying their conformational states and associated ligands.

  • 15.
    Olofsson, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Mr.
    Gharibyan, Anna (Contributor)
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Kristoffer, Brännström (Contributor)
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Solmaz, Golchin (Contributor)
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Pettersson, Nina
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Isabell, Hedberg
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Virta, Merit-Miriam (Contributor)
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Olofsson, Linnea (Contributor)
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Apolipoprotein E impairs amyloid-β fibril elongation and maturation2019In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, article id 10.1111/febs.15075Article in journal (Refereed)
    Abstract [en]

    Alzheimer's disease (AD) is strongly linked to amyloid depositions of the Aβ peptide (Aβ). The lipid-binding protein apolipoprotein E (ApoE) has been found to interfere with Aβ amyloid formation and to exert a strong clinical impact to the pathology of AD. The APOE gene exists in three allelic isoforms represented by APOE ε2, APOE ε3, and APOE ε4. Carriers of the APOE ε4 variant display a gene dose-dependent increased risk of developing the disease. Aβ amyloids are formed via a nucleation-dependent mechanism where free monomers are added onto a nucleus in a template-dependent manner. Using a combination of surface plasmon resonance and thioflavin-T assays, we here show that ApoE can target the process of fibril elongation and that its interference effectively prevents amyloid maturation. We expose a complex equilibrium where the concentration of ApoE, Aβ monomers, and the amount of already formed Aβ fibrils will affect the relative proportion and formation rate of mature amyloids versus alternative assemblies. The result illustrates a mechanism which may affect both the clearance rate of Aβ assemblies in vivo and the population of cytotoxic Aβ assemblies.

  • 16.
    Olofsson, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Lindhagen Persson, Malin
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Vestling, Monika
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Sauer-Eriksson, Elisabeth
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Öhman, Anders
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Quenched hydrogen/deuterium exchange NMR characterization of amyloid-β peptide aggregates formed in the presence of Cu2+ or Zn2+2009In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 276, no 15, p. 4051-4060Article in journal (Refereed)
    Abstract [en]

    Alzheimer's disease, a neurodegenerative disorder causing synaptic impairment and neuronal cell death, is strongly correlated with aggregation of the amyloid-β peptide (Aβ). Divalent metal ions such as Cu2+ and Zn2+ are known to significantly affect the rate of aggregation and morphology of Aβ assemblies in vitro and are also found at elevated levels within cerebral plaques in vivo. The present investigation characterized the architecture of the aggregated forms of Aβ(1–40) and Aβ(1–42) in the presence or absence of either Cu2+ or Zn2+ using quenched hydrogen/deuterium exchange combined with solution NMR spectroscopy. The NMR analyses provide a quantitative and residue-specific structural characterization of metal-induced Aβ aggregates, showing that both the peptide sequence and the type of metal ion exert an impact on the final architecture. Common features among the metal-complexed peptide aggregates are two solvent-protected regions with an intervening minimum centered at Asn27, and a solvent-accessible N-terminal region, Asp1–Lys16. Our results suggest that Aβ in complex with either Cu2+ or Zn2+ can attain an aggregation-prone β-strand–turn–β-strand motif, similar to the motif found in fibrils, but where the metal binding to the N-terminal region guides the peptide into an assembly distinctly different from the fibril form.

  • 17.
    Persson, Gerd
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Edlund, Håkan
    Lindblom, Göran
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Thermal behaviour of cubic phases rich in 1-monooleoyl-rac-glycerol in the ternary system: 1-monooleoyl-rac-glycerol/n-octyl-β-d-glucoside/water2003In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 270, no 1, p. 56-65Article in journal (Refereed)
    Abstract [en]

    Using synchrotron X-ray diffraction the thermal behaviour was studied of the cubic phases in the 1-monooleoyl-rac-glycerol (MO)/n-octyl-β-d-glucopyranoside (OG)/2H2O system with 58 or 45 wt % MO concentration and varying OG/2H2O contents. These MO contents correspond to a Pn3m cubic single-phase or a Pn3m cubic phase in excess water on the binary MO/water axis of the ternary phase diagram. The cubic liquid crystalline phases are stable with small fractions of OG, while higher OG concentrations trigger a cubic-to-lamellar phase transition. Moreover, with increasing OG concentration the initial Pn3m structure is completely converted to an Ia3d structure prior to the Lα phase being formed. Upon heating this effect is reversed, resulting in an Ia3d-to-Pn3m phase transition. For some samples additional peaks were observed in the diffractograms upon heating, resulting from the metastability notoriously shown by bicontinuous cubic phases. This judgement is supported by the fact that upon cooling these peaks were absent. Remarkably, both the Ia3d and the Pn3m cubic structures could be in equilibrium with excess water in this ternary system. A comparison is made with previous results on n-dodecyl-β-d-maltoside (DM), showing that cubic phases with OG have higher thermal and compositional stability than with DM.

  • 18.
    Rentoft, Matilda
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Kim, Kihoon
    Cho, Youngran
    Lee, Choon-Hwan
    Kim, AeRi
    Enhancer requirement for histone methylation linked with gene activation2008In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 275, no 23, p. 5994-6001Article in journal (Refereed)
    Abstract [en]

    Enhancers cause a high level of transcription and activation of chromatin structure at target genes. Hyperacetylation of histones H3 and H4, a mark of active chromatin, is established broadly across target loci by enhancers that function over long distances. In the present study, we studied the role of an enhancer in methylation of various lysine residues on H3 by comparing a model gene locus having an active enhancer with one in which the enhancer has been inactivated within the context of minichromosomes. The intact enhancer affected histone methylation at K4, K9 and K36 in distinct ways depending on the methylation level and the location in the locus. All three lysine residues were highly tri-methylated in the coding region of the gene linked to the active enhancer but not the inactive enhancer. However di-methylation of K9 and K36 was not affected by the enhancer. The enhancer region itself was marked by mono-methylation at K4 and K9, distinguishing it from the methyl marks in the gene coding region. These results indicate that an enhancer has roles in establishing active histone methylation patterns linked with gene transcription rather than removing methylation linked with gene inactivation.

  • 19.
    Sani, Marc-Antoine
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Castano, Sabine
    UMR 5248 CBMN, CNRS-Université Bordeaux, France.
    Dufourc, Erick J
    UMR 5248 CBMN, CNRS-Université Bordeaux, France.
    Gröbner, Gerhard
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Restriction of lipid motion in membranes triggered by β-sheet aggregation of the anti-apoptotic BH4 domain2008In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 275, no 3, p. 561-572Article in journal (Refereed)
    Abstract [en]

    The regulative BH4 domain of human Bcl-2 protein exerts its anti-apoptic activity via the mitochondrion. In the present study, we investigated the molecular interactions of this domain with negatively charged liposomes mimicking the outer mitochondrial membrane. To model the overproduction of Bcl-2 found in cancer processes, we studied the impact of elevated concentrations of its regulative BH4 segment on these mitochondrial membranes from the peptide and lipid perspective. Combined solid state 2H-NMR and differential scanning calorimetry revealed the coexistence of small sized fluid and rigid membrane domains over a large temperature range, which is confirmed by 31P-NMR at 30 °C. The latter are stabilized, in a cholesterol-like manner, by the presence of a BH4 peptide. In the same time scale, the reduction of the headgroup order is seen in the static 14N and 31P-NMR spectra when BH4 inserts into the bilayers. Indeed, attenuated total reflection spectroscopy indicated a dominant aggregated β-sheet secondary structure of BH4 with a 42° tilt relative to the membrane surface. These results are discussed in terms of membrane stabilization versus apoptotic mechanisms at the outer mitochondrial membrane location.

  • 20.
    Sattu, Kamaraj
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Hochgräfe, Falko
    Greifswald, Germany.
    Wu, Jianmin
    New South Wales, Australia.
    Umapathy, Ganesh
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Schönherr, Christina
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Ruuth, Kristina
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Chand, Damini
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Witek, Barbara
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Fuchs, James
    Columbus, OH, USA.
    Li, Pui-Kai
    Columbus, OH, USA.
    Hugosson, Fredrik
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Daly, Roger J.
    New South Wales, Australia; Victoria, Australia.
    Palmer, Ruth H.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Hallberg, Bengt
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Phosphoproteomic analysis of anaplastic lymphoma kinase (ALK) downstream signaling pathways identifies signal transducer and activator of transcription 3 as a functional target of activated ALK in neuroblastoma cells2013In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 280, no 21, p. 5269-5282Article in journal (Refereed)
    Abstract [en]

    Activation of the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase is a key oncogenic mechanism in a growing number of tumor types. In the majority of cases, ALK is activated by fusion with a dimerizing partner protein as a result of chromosomal translocation events, most studied in the case of the nucleophosmin-ALK and echinoderm microtubule-associated protein-like 4-ALK oncoproteins. It is now also appreciated that the full-length ALK receptor can be activated by point mutations and by deletions within the extracellular domain, such as those observed in neuroblastoma. Several studies have employed phosphoproteomics approaches to find substrates of ALK fusion proteins. In this study, we used MS-based phosphotyrosine profiling to characterize phosphotyrosine signaling events associated with the full-length ALK receptor. A number of previously identified and novel targets were identified. One of these, signal transducer and activator of transcription 3 (STAT3), has previously been observed to be activated in response to oncogenic ALK signaling, but the significance of this in signaling from the full-length ALK receptor has not been explored further. We show here that activated ALK robustly activates STAT3 on Tyr705 in a number of independent neuroblastoma cell lines. Furthermore, knockdown of STAT3 by RNA interference resulted in a reduction in myelocytomatosis neuroblastom (MYCN) protein levels downstream of ALK signaling. These observations, together with a decreased level of MYCN and inhibition of neuroblastoma cell growth in the presence of STAT3 inhibitors, suggest that activation of STAT3 is important for ALK signaling activity in neuroblastoma.

  • 21.
    Vaitkevicius, Karolis
    et al.
    Umeå University, Faculty of Medicine, Molecular Biology (Faculty of Medicine).
    Rompikuntal, Pramod Kumar
    Umeå University, Faculty of Medicine, Molecular Biology (Faculty of Medicine).
    Lindmark, Barbro
    Umeå University, Faculty of Medicine, Molecular Biology (Faculty of Medicine).
    Vaitkevicius, Rimas
    Song, Tianyan
    Umeå University, Faculty of Medicine, Molecular Biology (Faculty of Medicine).
    Wai, Sun Nyunt
    Umeå University, Faculty of Medicine, Molecular Biology (Faculty of Medicine).
    The metalloprotease PrtV from Vibrio cholerae2008In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 275, no 12, p. 3167-3177Article in journal (Refereed)
    Abstract [en]

    The Vibrio metalloprotease PrtV was purified from the culture supernatant of a Vibrio cholerae derivative that is deficient in several other secreted peptidases, including the otherwise abundant hemagglutinin/protease HapA. The PrtV is synthesized as a 102 kDa protein, but undergoes several N- and C-terminal processing steps during V. cholerae envelope translocation and prolonged incubation. Purified V. cholerae PrtV protease forms of 81 or 73 kDa were stabilized by calcium ions. Removal of calcium resulted in further rapid autoproteolysis. The two major products of autoproteolysis of the PrtV protease were approximately 37 and 18 kDa and could not be separated under non-denaturing conditions, indicating they are interacting domains. In an assay using cultured cells of the human intestinal cell line HCT8, the PrtV protein showed a cytotoxic effect leading to cell death. Using human blood plasma as a source of potential substrates of mammalian origin for the PrtV protease, we found that the extracellular matrix components fibronectin and fibrinogen were degraded by the enzyme. Additional tests with individual protein substrates revealed that plasminogen was also a possible target for the PrtV protease.

  • 22.
    Wikström Hultdin, Ulrika
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Lindberg, Stina
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Grundström, Christin
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Huang, Shenghua
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Uhlin, Bernt Eric
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Sauer-Eriksson, Elisabeth
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Structure of FocB: a member of a family of transcription factors regulating fimbrial adhesin expression in uropathogenic Escherichia coli2010In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 277, no 16, p. 3368-3381Article in journal (Refereed)
    Abstract [en]

    In uropathogenic Escherichia coli, UPEC, different types of fimbriae are expressed in order to mediate interactions with host tissue. FocB belongs to the PapB family of transcription factors involved in the regulation of fimbriae gene clusters. Recent findings suggest that members from this family of proteins may form different protein-protein complexes and that they may exert both positive and negative effects on transcription of fimbriae genes. To elucidate the detailed function of FocB, we have determined its crystal structure at 1.4 Å resolution. FocB is an all alpha helical structure with a helix-turn-helix (HTH) motif. Interestingly, conserved residues important for DNA-binding are not located in the recognition helix of the HTH-motif, but in the preceding helix. Results from protein-DNA binding studies indicated that FocB interacts with minor groove of its cognate DNA, which also points to a DNA-interaction unusual for this motif. Packing interactions in the crystals gave two plausible dimerization interfaces. Conserved residues known to be important for protein oligomerization are present at both interfaces, suggesting that both sites play a role in a functional FocB protein.

  • 23.
    Wilhelm, Kristina
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Darinskas, A
    Noppe, W
    Duchardt, E
    Mok, KH
    Vukojevic, V
    Schleucher, Jürgen
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Morozova-Roche, Ludmilla
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Protein oligomerization induced by oleic acid at the solidliquid interface: equine lysozyme cytotoxic complexes2009In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 276, no 15, p. 3975-3989Article in journal (Refereed)
    Abstract [en]

    Protein oligomeric complexes have emerged as a major target of current research because of their key role in aggregation processes in living systems and in vitro. Hydrophobic and charged surfaces may favour the self-assembly process by recruiting proteins and modifying their interactions. We found that equine lysozyme assembles into multimeric complexes with oleic acid (ELOA) at the solid–liquid interface within an ion-exchange chromatography column preconditioned with oleic acid. The properties of ELOA were characterized using NMR, spectroscopic methods and atomic force microscopy, and showed similarity with both amyloid oligomers and the complexes with oleic acid and its structural homologous protein α-lactalbumin, known as humanα-lactalbumin made lethal for tumour cells (HAMLET). As determined by NMR diffusion measurements, ELOA may consist of 4–30 lysozyme molecules. Each lysozyme molecule is able to bind 11–48 oleic acids in various preparations. Equine lysozyme acquired a partially unfolded conformation in ELOA, as evident from its ability to bind hydrophobic dye 8-anilinonaphthalene-1-sulfonate. CD and NMR spectra. Similar to amyloid oligomers, ELOA also interacts with thioflavin-T dye, shows a spherical morphology, assembles into ring-shaped structures, as monitored by atomic force microscopy, and exerts a toxic effect in cells. Studies of well-populated ELOA shed light on the nature of the amyloid oligomers and HAMLET complexes, suggesting that they constitute one large family of cytotoxic proteinaceous species. The hydrophobic surfaces can be used profitably to produce complexes with very distinct properties compared to their precursor proteins.

  • 24.
    Yasmin, Lubna
    et al.
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Jansson, Anna L
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Panahandeh, Tooba
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Palmer, Ruth H
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Pathogenesis (UCMP) (Faculty of Medicine).
    Francis, Matthew S
    Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Science and Technology, Molecular Biology (Faculty of Science and Technology).
    Hallberg, Bengt
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Delineation of exoenzyme S residues that mediate the interaction with 14-3-3 and its biological activity.2006In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 273, no 3, p. 638-646Article in journal (Refereed)
1 - 24 of 24
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf