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FEBS Journal

Cover image for Vol. 279 Issue 19

October 2012

Volume 279, Issue 19

Pages 3529–3763

  1. Minireview Series

    1. Top of page
    2. Minireview Series
    3. Minireview
    4. Review Article
    5. Original Articles
    6. Corrigendum
    7. Author index
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      PDZ-containing proteins as targets in human pathologies (page 3529)

      Daniela Gardiol

      Article first published online: 29 AUG 2012 | DOI: 10.1111/j.1742-4658.2012.08685.x

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      PDZ domains are very abundant protein interaction domains widespread in nature. A large amount of evidence has underscored the importance of the PDZ interactions in the control of intracellular pathways whose abnormal regulation may lead to the development of several pathologies. This series of minireviews covers different aspects of human PDZ-containing proteins, underlining and discussing new concepts and findings.

  2. Minireview

    1. Top of page
    2. Minireview Series
    3. Minireview
    4. Review Article
    5. Original Articles
    6. Corrigendum
    7. Author index
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      Human papillomaviruses and the specificity of PDZ domain targeting (pages 3530–3537)

      David Pim, Martina Bergant, Siaw S. Boon, Ketaki Ganti, Christian Kranjec, Paola Massimi, Vanitha K. Subbaiah, Miranda Thomas, Vjekoslav Tomaić and Lawrence Banks

      Article first published online: 29 AUG 2012 | DOI: 10.1111/j.1742-4658.2012.08709.x

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      This review highlights those interactions of the high-risk human papillomavirus E6 oncoproteins with cellular PDZ domain-containing proteins that are involved in the regulation of processes associated with the control of cell attachment, cell proliferation, cell polarity and cell signaling. Through these interactions, the E6 oncoproteins modulate cellular substrate function, helping to bring about and maintain HPV-induced malignancy.

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      Differential expression of PDZ domain-containing proteins in human diseases – challenging topics and novel issues (pages 3538–3548)

      Florencia Facciuto, Ana L. Cavatorta, Marina Bugnon Valdano, Federico Marziali and Daniela Gardiol

      Article first published online: 29 AUG 2012 | DOI: 10.1111/j.1742-4658.2012.08699.x

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      In the present review we discuss the regulation of the expression of certain PDZ polarity proteins which are localized at intercellular junctions. We also provide a critical overview of recent findings about the role of these proteins during the development of human diseases. The understanding of these issues would be valuable for the design of novel therapeutic intervention for common pathologies, such as cancer.

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      The PDZ protein discs-large (DLG): the ‘Jekyll and Hyde’ of the epithelial polarity proteins (pages 3549–3558)

      Sally Roberts, Craig Delury and Elizabeth Marsh

      Article first published online: 29 AUG 2012 | DOI: 10.1111/j.1742-4658.2012.08729.x

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      Disturbance of the function of the multi-PDZ domain-containing protein DLG in Drosophila leads to uncontrolled epithelial cell proliferation and neoplastic transformation, thereby defining DLG as a potential tumour suppressor. Here, we examine the biological functions of the mammalian homologues of DLG, focussing on DLG1, and highlight recent findings that imply DLG1 as having both tumour suppressor and paradoxically, oncogenic functions depending on the precise cellular context

  3. Review Article

    1. Top of page
    2. Minireview Series
    3. Minireview
    4. Review Article
    5. Original Articles
    6. Corrigendum
    7. Author index
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      Regulation of self-renewal in normal and cancer stem cells (pages 3559–3572)

      Maria V. Verga Falzacappa, Chiara Ronchini, Linsey B. Reavie and Pier G. Pelicci

      Article first published online: 24 AUG 2012 | DOI: 10.1111/j.1742-4658.2012.08727.x

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      It has been shown that only a small sub-population of cells, the cancer stem cells (CSCs), is necessary and sufficient to originate a tumour. We discuss how, compared to normal SCs, CSCs exhibit a profound de-regulation of their self-renewal capability, mainly due to differences in mode of division, cell-cycle properties, replicative potential and handling of DNA-damage.

  4. Original Articles

    1. Top of page
    2. Minireview Series
    3. Minireview
    4. Review Article
    5. Original Articles
    6. Corrigendum
    7. Author index
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      N-terminal cleavage fragment of focal adhesion kinase is required to activate the survival signalling pathway in cultured myoblasts under oxidative stress (pages 3573–3583)

      Jeong A Lim, Sung Ho Hwang, Min Jeong Kim, Sang Soo Kim and Hye Sun Kim

      Article first published online: 16 AUG 2012 | DOI: 10.1111/j.1742-4658.2012.08715.x

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      Cleavage of focal adhesion kinase (FAK) by calpain to produce N-terminal FAK (N-FAK) is suppressed under oxidative stress in cultured myoblasts. Calpeptin, a calpain inhibitor, reduced cell survival whereas overexpression of N-FAK activated cell survival signaling under oxidative stress. These results suggest that N-FAK is closely related to survival signaling in myoblasts under oxidative stress.

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      Roles of heterotypic CCN2/CTGF–CCN3/NOV and homotypic CCN2–CCN2 interactions in expression of the differentiated phenotype of chondrocytes (pages 3584–3597)

      Mitsuhiro Hoshijima, Takako Hattori, Eriko Aoyama, Takashi Nishida, Takashi Yamashiro and Masaharu Takigawa

      Article first published online: 28 AUG 2012 | DOI: 10.1111/j.1742-4658.2012.08717.x

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      To identify proteins that regulate CCN2 activity in chondrocytes, yeast two-hybrid screenings identified CCN2 and CCN3, and their binding domains were estimated. Direct binding between CCN2 and CCN3 was confirmed in vitro and in vivo. CCN2 enhanced, whereas CCN3 inhibited, the expression of cartilaginous matrix genes; and the combined treatment with CCN2 and CCN3 abolished the inhibitory effect by CCN3.

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      Functional roles of H98 and W99 and β2α2 loop dynamics in the α-l-arabinofuranosidase from Thermobacillus xylanilyticus (pages 3598–3611)

      Faten Arab-Jaziri, Bastien Bissaro, Sophie Barbe, Olivier Saurel, Hélène Débat, Claire Dumon, Virginie Gervais, Alain Milon, Isabelle André, Régis Fauré and Michael J. O’Donohue

      Article first published online: 31 AUG 2012 | DOI: 10.1111/j.1742-4658.2012.08720.x

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      Experimentation and in silico analyses have revealed that during catalysis the β2α2 loop in the α-l-arabinofuranosidase from Thermobacillus xylanilyticus undergoes a large movement, which leads to the relocation of W99 and the formation of subsite-1. Similarly, the relocation of H98 contributes to the definition of a catalytically-operational active site, at least in l-arabinofuranosidases that display a histidine at this position.

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      The role of conserved inulosucrase residues in the reaction and product specificity of Lactobacillus reuteri inulosucrase (pages 3612–3621)

      Munir A. Anwar, Hans Leemhuis, Tjaard Pijning, Slavko Kralj, Bauke W. Dijkstra and Lubbert Dijkhuizen

      Article first published online: 3 SEP 2012 | DOI: 10.1111/j.1742-4658.2012.08721.x

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      The structurally highly similar levansucrase and inulosucrase enzymes differ significantly in their product profiles and activity levels. Site-directed mutagenesis of highly conserved inulosucrase residues in Lactobacillus reuteri 121 Inu and comparison with the 3D structure of InuJ showed that the amino acid residues located in blade 4, including a unique helix α7, have clear effects on transglycosylation activity and FOS product spectrum.

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      The influence of identity elements on the aminoacylation of tRNAArg by plant and Escherichia coli arginyl-tRNA synthetases (pages 3622–3638)

      Carolin A. Aldinger, Anne-Katrin Leisinger and Gabor L. Igloi

      Article first published online: 3 SEP 2012 | DOI: 10.1111/j.1742-4658.2012.08722.x

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      Identity elements for arginine and canavanine charging of plant tRNAArg by cognate arginyl-tRNA synthetase have been determined and compared to the E. coli system. Transplantation of these features into non-cognate tRNAs reveals the existence of additional and of cryptic recognition elements. Amino acid discrimination between arginine and canavanine may be manipulated by sequence changes at different sites within the tRNA structure.

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      Crystal structure and chitin oligosaccharide-binding mode of a ‘loopful’ family GH19 chitinase from rye, Secale cereale, seeds (pages 3639–3651)

      Takayuki Ohnuma, Tomoyuki Numata, Takuo Osawa, Hideko Inanaga, Yoko Okazaki, Shoko Shinya, Kaori Kondo, Tatsuya Fukuda and Tamo Fukamizo

      Article first published online: 3 SEP 2012 | DOI: 10.1111/j.1742-4658.2012.08723.x

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      Crystal structure of a ‘loopful’ GH19 chitinase from rye seeds in a complex with an N-acetylglucosamine tetramer, (GlcNAc)4, was solved, and revealed the binding mode of the tetramer to subsites +1, +2, +3, and +4. HPLC analysis of the reaction products and (GlcNAc)4 titration experiments using NMR spectroscopy confirmed the binding mode obtained by the crystallographic analysis.

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      Growth arrest-specific gene 1 is downregulated and inhibits tumor growth in gastric cancer (pages 3652–3664)

      Honghong Wang, Xiong Zhou, Yongguo Zhang, Hongwu Zhu, Lina Zhao, Linni Fan, Yingmei Wang, Yi Gang, Kaichun Wu, Zhiguo Liu and Daiming Fan

      Article first published online: 31 AUG 2012 | DOI: 10.1111/j.1742-4658.2012.08726.x

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      Gastric cancer is a serious danger to the mankind. We found that GAS1 was decreased in gastric cancer and predicted poor prognosis. Restoration of GAS1 could inhibit cell growth and promote apoptosis of gastric cancer cells at least through modulating Bcl-2/Bax ratio and activating caspase-3, which suggest that GAS1 might be used as a novel therapeutic candidate for gastric cancer.

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      An anionic synthetic sugar containing 6-SO3-NAcGlc mimics the sulfated cruzipain epitope that plays a central role in immune recognition (pages 3665–3679)

      Alicia S. Couto, Luciana L. Soprano, Malena Landoni, Marilyne Pourcelot, Diana M. Acosta, Laurent Bultel, Juliana Parente, Maximiliano R. Ferrero, Maximilien Barbier, Christophe Dussouy, Mónica I. Esteva, José Kovensky and Vilma G. Duschak

      Article first published online: 4 SEP 2012 | DOI: 10.1111/j.1742-4658.2012.08728.x

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      A systematic study of the chemical characteristics needed for antibody binding to the cruzipain sulfated epitope was performed by immunoassays. Different molecules were synthesized, coupled to BSA/aprotinin, and confronted with rabbit/mice sera specific for Cz/C-T and purified IgGs from immune and human Chagas disease sera, demonstrating that synthetic GlcNAc6S mimics the N-glycan-linked-sulfated epitope displayed in the C-T domain of natural cruzipain.

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      pH-dependent structural conformations of B-phycoerythrin from Porphyridium cruentum (pages 3680–3691)

      Ana Camara-Artigas, Julio Bacarizo, Montserrat Andujar-Sanchez, Emilia Ortiz-Salmeron, Concepcion Mesa-Valle, Celia Cuadri, Jose M. Martin-Garcia, Sergio Martinez-Rodriguez, Tania Mazzuca-Sobczuk, Maria J. Ibañez and James P. Allen

      Article first published online: 4 SEP 2012 | DOI: 10.1111/j.1742-4658.2012.08730.x

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      We have crystallized the B-phycoerythrin from the red algae Porphyridium cruentum at the pH 5 and 8. The quality of the measured diffraction data has allowed us to perform a detailed modeling of the cofactors and the solvent, enabling the detection of some changes that are proposed to be important for the function of this protein as a light-harvesting system

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      The Escherichia coli GTPase ObgE modulates hydroxyl radical levels in response to DNA replication fork arrest (pages 3692–3704)

      Cyrielle I. Kint, Natalie Verstraeten, Inez Wens, Veerle R. Liebens, Johan Hofkens, Wim Versées, Maarten Fauvart and Jan Michiels

      Article first published online: 31 AUG 2012 | DOI: 10.1111/j.1742-4658.2012.08731.x

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      In this study, the structure-function relationship of the essential GTPase ObgE with regard to sensitivity to stalled replication forks was analysed in Escherichia coli. Several mutant obgE alleles were identified that conferred a dominant negative effect upon treatment with the replication inhibitor hydroxyurea. Further analysis revealed the involvement of hydroxyl radical toxicity in the observed ObgE-mediated effects.

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      Mapping the interaction between the cytoplasmic domains of HIV-1 viral protein U and human CD4 with NMR spectroscopy (pages 3705–3714)

      Sameer K. Singh, Luis Möckel, Pallavi Thiagarajan-Rosenkranz, Marc Wittlich, Dieter Willbold and Bernd W. Koenig

      Article first published online: 31 AUG 2012 | DOI: 10.1111/j.1742-4658.2012.08732.x

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      Downregulation of the main HIV-1 receptor CD4 from the surface of infected cells by the viral protein U (VpU) involves the binding of VpU to newly synthesized CD4 in the endoplasmic reticulum. Regions in the cytoplasmic domain of VpU involved in CD4 binding were identified by NMR spectroscopy. VpU binds to a membrane proximal region in the cytoplasmic domain of CD4

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      Homeodomain-containing protein HOXB9 regulates expression of growth and angiogenic factors, facilitates tumor growth in vitro and is overexpressed in breast cancer tissue (pages 3715–3726)

      Bishakha Shrestha, Khairul I. Ansari, Arunoday Bhan, Sahba Kasiri, Imran Hussain and Subhrangsu S. Mandal

      Article first published online: 31 AUG 2012 | DOI: 10.1111/j.1742-4658.2012.08733.x

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      The homeobox gene HOXB9 is essential for mammary gland and sternum development and is involved in angiogenesis. Our studies demonstrated that HOXB9 is overexpressed in breast cancer tissue. HOXB9 plays crucial roles in cell cycle progression and in tumorigenesis. HOXB9 regulates expression of various tumor growth and angiogenic factors and 3D colony formation via its homodomain

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      Requirement of lid2 for interfacial activation of a family I.3 lipase with unique two lid structures (pages 3727–3737)

      Maria Cheng, Clement Angkawidjaja, Yuichi Koga and Shigenori Kanaya

      Article first published online: 31 AUG 2012 | DOI: 10.1111/j.1742-4658.2012.08734.x

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      Pseudomonas sp. MIS38 lipase (PML) is characterized by the presence of two lids (lid1 and lid2). Characterization of the PML derivative without lid2 indicates that lid2 is required for interfacial activation of PML. We propose that hydrophobic surface area provided by lid1 and lid2 is necessary to hold the micellar substrates firmly to the active site

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      NMR investigations of the dual targeting peptide of Thr-tRNA synthetase and its interaction with the mitochondrial Tom20 receptor in Arabidopsis thaliana (pages 3738–3748)

      Weihua Ye, Erika Spånning, Sofia Unnerståle, David Gotthold, Elzbieta Glaser and Lena Mäler

      Article first published online: 31 AUG 2012 | DOI: 10.1111/j.1742-4658.2012.08735.x

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      Protein targeting is usually specific, but several plant proteins are dually targeted into mitochondria and chloroplasts. We present NMR studies of a dual targeting peptide and its interaction with Tom20. The targeting peptide is mostly unstructured, with a propensity to form an α-helical structure in one region, S6-F27. Two regions are important for Tom20 recognition, which appears to be highly dynamic

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      Expression of human CYP27B1 in Escherichia coli and characterization in phospholipid vesicles (pages 3749–3761)

      Edith K. Y. Tang, Elaine W. Tieu and Robert C. Tuckey

      Article first published online: 28 AUG 2012 | DOI: 10.1111/j.1742-4658.2012.08736.x

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      Human CYP27B1 was expressed in E. coli, partially purified and characterised in a reconstituted phospholipid membrane. Parameters examined included adrenodoxin concentration, phospholipid composition and secosteroid side-chain structure. We showed that human CYP27B1 is active towards a range of substrates including 25-hydroxyvitamins D3 and D2, and 24R,25-dihydroxyvitamin D3 in phospholipid vesicles, with some substrates causing inhibition at high concentrations.

  5. Corrigendum

    1. Top of page
    2. Minireview Series
    3. Minireview
    4. Review Article
    5. Original Articles
    6. Corrigendum
    7. Author index
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      Corrigendum (page 3762)

      Article first published online: 3 SEP 2012 | DOI: 10.1111/j.1742-4658.2012.08740.x

      This article corrects:
  6. Author index

    1. Top of page
    2. Minireview Series
    3. Minireview
    4. Review Article
    5. Original Articles
    6. Corrigendum
    7. Author index
    1. You have free access to this content
      Author index (page 3763)

      Article first published online: 17 SEP 2012 | DOI: 10.1111/j.1742-4658.2012.08339.x

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