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The EMBO Journal
Stalling in mitosis and releasing the apoptotic brake
Thu, 07/22/2010 - 02:00Stalling in mitosis and releasing the apoptotic brake
The EMBO Journal 29, 2255 (2010). doi:10.1038/emboj.2010.150
Authors: Manabu Kurokawa & Sally Kornbluth
EMBO J2914, 2407–2420 (2010); published online 4 June 2010Microtubule poisons induce mitotic arrest that leads to apoptotic cell death if not resolved in a timely manner, but the mechanisms that directly link this cell cycle arrest to apoptosis have been elusive. In this issue of The EMBO Journal, Clarke and colleagues show that Mcl-1, an anti-apoptotic Bcl-2 family protein, is phosphorylated by the mitotic kinase CDK1/cyclin B1. This targets the protein for degradation by anaphase-promoting complex/cyclosome (APC/C)-mediated ubiquitination, in a manner such that only prolonged arrest allows sufficient Mcl-1 phosphorylation and degradation to trigger apoptosis. Thus, the APC/C, a major effector of the spindle assembly checkpoint (SAC), not only ensures cell cycle arrest upon spindle disruption, but promotes cell death when the duration of mitotic arrest is too long.
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Cell polarity/motility in bacteria: closer to eukaryotes than expected?
Thu, 07/22/2010 - 02:00Cell polarity/motility in bacteria: closer to eukaryotes than expected?
The EMBO Journal 29, 2258 (2010). doi:10.1038/emboj.2010.144
Author: Emilia M F Mauriello
EMBO J2914, 2276–2289 (2010); published online 11 June 2010The Gram-negative bacterium Myxococcus xanthus glides on solid surfaces and periodically reverses the direction of movement. Work published in this issue of The EMBO Journal (Leonardy et al, 2010) reports on the small GTPase MglA that ensures the correct polarity of the motility engines through its GTP/GDP cycle in conjunction with its cognate GAP, MglB. MglA has also been shown to interact with the actin-like protein MreB in eukaryotic-like motility complexes. Altogether, the data suggest that compelling similarities exist between the mechanisms of motility and establishment of cell polarity in M. xanthus and eukaryotes.
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Twins take the job
Thu, 07/22/2010 - 02:00Twins take the job
The EMBO Journal 29, 2260 (2010). doi:10.1038/emboj.2010.148
Authors: María-Eugenia Gas & Bertrand Séraphin
EMBO J2914, 2358–2367 (2010); published online 8 June 2010EMBO J2914, 2342–2357 (2010); published online 8 June 2010The exosome, one of the main cellular ribonucleases in eukaryotes, is a multi-subunit complex of deep evolutionary origin. This complex has been extensively characterized in Saccharomyces cerevisae. Given the good conservation of exosome subunit sequences, it was widely accepted that the yeast exosome provided a good model for other eukaryotic species. Recent analysis of higher eukaryotic exosomes reveals some differences challenging this idea. In this issue of The EMBO Journal, Tomecki et al (2010) and Staals et al (2010) provide new insights into the composition and function of the human exosome, with implications for our understanding on the organization, function and localization of this complex in these cells.
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Channels get in an HUFA: RNA editing gets them out of a jam
Thu, 07/08/2010 - 02:00Channels get in an HUFA: RNA editing gets them out of a jam
The EMBO Journal 29, 2097 (2010). doi:10.1038/emboj.2010.134
Authors: Richard Horn & Robert Reenan
EMBO J2913, 2101–2113 (2010); published online 11 May 2010The enzymatic conversion of adenosine-to-inosine (A-to-I) in RNA rewrites the informational output of a number of different classes of coding and non-coding RNA transcripts. In this issue, Decher et al (2010) reveal a new functional consequence for an ancient RNA editing site in certain animal voltage-gated K+ channel (Kv) genes. Abundant highly unsaturated fatty acids (HUFAs), which are essential in mammals for normal brain function, block conduction of Kv channels—an effect that can be nearly obliterated by the recoding of a single amino acid through RNA editing.
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Receptor endocytosis: Frizzled joins the ubiquitin club
Thu, 07/08/2010 - 02:00Receptor endocytosis: Frizzled joins the ubiquitin club
The EMBO Journal 29, 2099 (2010). doi:10.1038/emboj.2010.132
Author: Ken M Cadigan
EMBO J2913, 2114–2125 (2010); published online 14 May 2010Wnt/β-catenin signalling is initiated by binding of secreted Wnt ligands to Frizzled and LRP5/6/Arrow co-receptors. A new study in this issue of The EMBO Journal provides compelling evidence that the level of cell surface Frizzled is controlled by a cycle of mono-ubiquitylation–deubiquitylation, the latter being mediated by the deubiquitylating enzyme UBPY/USP8. The amount of Frizzled on the plasma membrane appears to be a major rate-limiting factor in determining a cell's Wnt responsiveness.
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The NoRC complex mediates heterochromatin formation and stability of silent rRNA genes and centromeric repeats
Thu, 07/08/2010 - 02:00The NoRC complex mediates heterochromatin formation and stability of silent rRNA genes and centromeric repeats
The EMBO Journal 29, 2253 (2010). doi:10.1038/emboj.2010.145
Authors: Claudio Guetg, Philipp Lienemann, Valentina Sirri, Ingrid Grummt, Danièle Hernandez-Verdun, Michael O Hottiger, Martin Fussenegger & Raffaella Santoro
Correction to:The EMBO Journal (2010) 29, 2135–2146. doi:10.1038/emboj.2010.17; Published online 18 February 2010The author list of the online version of the above paper by Guetg et al was incorrect. Martin Fussenegger's authorship was
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Crystal structure of the yeast Sac1: implications for its phosphoinositide phosphatase function
Thu, 07/01/2010 - 23:00Crystal structure of the yeast Sac1: implications for its phosphoinositide phosphatase function
The EMBO Journal 29, 2472 (2010). doi:10.1038/emboj.2010.146
Authors: Andrew Manford, Tian Xia, Ajay Kumar Saxena, Christopher Stefan, Fenghua Hu, Scott D Emr & Yuxin Mao
Correction to: The EMBO Journal (2010) 29, 1489–1498; doi:10.1038/emboj.2010.57In the above article, the authors omitted the current affiliation of Dr Ajay Kumar Saxena, which is: Structural Biology Lab, School of Life Sciences, Jawaharlal Nehru University,
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P2X4 receptors mediate PGE2 release by tissue-resident macrophages and initiate inflammatory pain
Thu, 06/17/2010 - 23:00P2X4 receptors mediate PGE2 release by tissue-resident macrophages and initiate inflammatory pain
The EMBO Journal 29, 2290 (2010). doi:10.1038/emboj.2010.126
Authors: Lauriane Ulmann, Hélène Hirbec & François Rassendren
Prostaglandin E2 (PGE2) is a key mediator of inflammation and contributes to pain hypersensitivity by promoting sensory neurons hyperexcitability. PGE2 synthesis results from activation of a multi-step enzymatic cascade that includes cyclooxygenases (COXs), the main targets of non-steroidal anti-inflammatory drugs (NSAIDs). Although NSAIDs are widely
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Cooperative interactions at the SLP-76 complex are critical for actin polymerization
Thu, 06/17/2010 - 23:00Cooperative interactions at the SLP-76 complex are critical for actin polymerization
The EMBO Journal 29, 2315 (2010). doi:10.1038/emboj.2010.133
Authors: Mira Barda-Saad, Naoto Shirasu, Maor H Pauker, Nirit Hassan, Orly Perl, Andrea Balbo, Hiroshi Yamaguchi, Jon C D Houtman, Ettore Appella, Peter Schuck & Lawrence E Samelson
T-cell antigen receptor (TCR) engagement induces formation of multi-protein signalling complexes essential for regulating T-cell functions. Generation of a complex of SLP-76, Nck and VAV1 is crucial for regulation of the actin machinery. We define the composition, stoichiometry and specificity of interactions in the SLP-76,
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The ATAC acetyl transferase complex controls mitotic progression by targeting non-histone substrates
Thu, 06/17/2010 - 23:00The ATAC acetyl transferase complex controls mitotic progression by targeting non-histone substrates
The EMBO Journal 29, 2381 (2010). doi:10.1038/emboj.2010.125
Authors: Meritxell Orpinell, Marjorie Fournier, Anne Riss, Zita Nagy, Arnaud R Krebs, Mattia Frontini & Làszlò Tora
All DNA-related processes rely on the degree of chromatin compaction. The highest level of chromatin condensation accompanies transition to mitosis, central for cell cycle progression. Covalent modifications of histones, mainly deacetylation, have been implicated in this transition, which also involves transcriptional repression. Here, we show
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CaMKII hunkers down on the muscarinic M4 receptor to help curb cocaine-induced hyperlocomotion
Thu, 06/17/2010 - 02:00CaMKII hunkers down on the muscarinic M4 receptor to help curb cocaine-induced hyperlocomotion
The EMBO Journal 29, 1943 (2010). doi:10.1038/emboj.2010.105
Authors: Ivar S Stein & Johannes W Hell
EMBO J2912, 2070–2081 (2010); published online 11 May 2010The dopaminergic receptor D1 activates and the muscarinic acetylcholine receptor (mAChR) M4 inhibits adenylyl cyclase (AC) and thereby cAMP production through the trimeric Gαs and Gαi/o proteins, respectively (Wess et al, 2007). D1 and M4 are coexpressed in striatal output neurons, where M4 antagonizes D1 signalling as recently pinpointed by conditional M4 knockout in D1-expressing neurons (Jeon et al, 2010). Closely following on the heels of this article, Guo et al (2010) report in this issue that CaMKII binds and phosphorylates M4 upon Ca2+ influx to augment the antagonistic action of M4 on D1 signalling and on D1-mediated, cocaine-triggered hyperlocomotion.
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How do tumours adapt to nutrient stress?
Thu, 06/17/2010 - 02:00How do tumours adapt to nutrient stress?
The EMBO Journal 29, 1946 (2010). doi:10.1038/emboj.2010.110
Authors: Ronald C Wek & Kirk A Staschke
EMBO J2912, 2082–2096 (2010); published online 14 May 2010Reduced blood flow contributes to tumour hypoxia and nutrient deprivation forcing cancer cells to adapt to ensure survival. In this issue of The EMBO Journal, Ye et al show that a stress response pathway including the eIF2 kinase GCN2 and its downstream target, the transcriptional activator ATF4, is critical for proliferation and survival of tumour cells after starvation for amino acids or glucose and is essential for growth in vivo in a xenograft model. This study provides new mechanistic insight into how tumour cells sense and adapt to nutrient restriction and suggests new approaches for cancer chemotherapy.
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A classical NLS and the SUN domain contribute to the targeting of SUN2 to the inner nuclear membrane
Mon, 06/14/2010 - 23:00A classical NLS and the SUN domain contribute to the targeting of SUN2 to the inner nuclear membrane
The EMBO Journal 29, 2262 (2010). doi:10.1038/emboj.2010.119
Authors: Yagmur Turgay, Rosemarie Ungricht, Andrea Rothballer, Alexa Kiss, Gabor Csucs, Peter Horvath & Ulrike Kutay
Integral membrane proteins of the inner nuclear membrane (INM) are inserted into the endoplasmic reticulum membrane during their biogenesis and are then targeted to their final destination. We have used human SUN2 to delineate features that are required for INM targeting and have identified multiple
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Ezrin tunes T-cell activation by controlling Dlg1 and microtubule positioning at the immunological synapse
Mon, 06/14/2010 - 23:00Ezrin tunes T-cell activation by controlling Dlg1 and microtubule positioning at the immunological synapse
The EMBO Journal 29, 2301 (2010). doi:10.1038/emboj.2010.127
Authors: Rémi Lasserre, Stéphanie Charrin, Céline Cuche, Anne Danckaert, Maria-Isabel Thoulouze, Fabrice de Chaumont, Tarn Duong, Nathalie Perrault, Nadine Varin-Blank, Jean-Christophe Olivo-Marin, Sandrine Etienne-Manneville, Monique Arpin, Vincenzo Di Bartolo & Andrés Alcover
T-cell receptor (TCR) signalling is triggered and tuned at immunological synapses by the generation of signalling complexes that associate into dynamic microclusters. Microcluster movement is necessary to tune TCR signalling, but the molecular mechanism involved remains poorly known. We show here that the membrane-microfilament linker
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TCR-mediated ThPOK induction promotes development of mature (CD24−) γδ thymocytes
Mon, 06/14/2010 - 23:00TCR-mediated ThPOK induction promotes development of mature (CD24−) γδ thymocytes
The EMBO Journal 29, 2329 (2010). doi:10.1038/emboj.2010.113
Authors: Kyewon Park, Xi He, Hyung-Ok Lee, Xiang Hua, Yi Li, David Wiest & Dietmar J Kappes
T lymphocytes develop into two major lineages characterized by expression of the αβ and γδ T cell receptor (TCR) heterodimers. Within each major lineage, further specialization occurs, resulting in distinct subsets that differ in TCR specificity, phenotype and functional attributes. Thus, in the murine thymus,
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CIN85 regulates dopamine receptor endocytosis and governs behaviour in mice
Mon, 06/14/2010 - 23:00CIN85 regulates dopamine receptor endocytosis and governs behaviour in mice
The EMBO Journal 29, 2421 (2010). doi:10.1038/emboj.2010.120
Authors: Noriaki Shimokawa, Kaisa Haglund, Sabine M Hölter, Caroline Grabbe, Vladimir Kirkin, Noriyuki Koibuchi, Christian Schultz, Jan Rozman, Daniela Hoeller, Chun-Hong Qiu, Marina B Londoño, Jun Ikezawa, Peter Jedlicka, Birgit Stein, Stephan W Schwarzacher, David P Wolfer, Nicole Ehrhardt, Rainer Heuchel, Ioannis Nezis, Andreas Brech, Mirko H H Schmidt, Helmut Fuchs, Valerie Gailus-Durner, Martin Klingenspor, Oliver Bogler, Wolfgang Wurst, Thomas Deller, Martin Hrabé de Angelis & Ivan Dikic
Despite extensive investigations of Cbl-interacting protein of 85 kDa (CIN85) in receptor trafficking and cytoskeletal dynamics, little is known about its functions in vivo. Here, we report the study of a mouse deficient of the two CIN85 isoforms expressed in the central nervous system,
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SNMIB/Apollo protects leading-strand telomeres against NHEJ-mediated repair
Mon, 06/14/2010 - 23:00SNMIB/Apollo protects leading-strand telomeres against NHEJ-mediated repair
The EMBO Journal 29, 2230 (2010). doi:10.1038/emboj.2010.58
Authors: Yung C Lam, Shamima Akhter, Peili Gu, Jing Ye, Anaïs Poulet, Marie-Josèphe Giraud-Panis, Susan M Bailey, Eric Gilson, Randy J Legerski & Sandy Chang
Progressive telomere attrition or deficiency of the protective shelterin complex elicits a DNA damage response as a result of a cell's inability to distinguish dysfunctional telomeric ends from DNA double-strand breaks. SNMIB/Apollo is a shelterin-associated protein and a member of the SMN1/PSO2 nuclease family that
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Regulation of dynamic polarity switching in bacteria by a Ras-like G-protein and its cognate GAP
Thu, 06/10/2010 - 23:00Regulation of dynamic polarity switching in bacteria by a Ras-like G-protein and its cognate GAP
The EMBO Journal 29, 2276 (2010). doi:10.1038/emboj.2010.114
Authors: Simone Leonardy, Mandy Miertzschke, Iryna Bulyha, Eva Sperling, Alfred Wittinghofer & Lotte Søgaard-Andersen
The rod-shaped cells of the bacterium Myxococcus xanthus move uni-directionally and occasionally undergo reversals during which the leading/lagging polarity axis is inverted. Cellular reversals depend on pole-to-pole relocation of motility proteins that localize to the cell poles between reversals. We show that MglA is
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The C-terminal α–α superhelix of Pat is required for mRNA decapping in metazoa
Thu, 06/10/2010 - 23:00The C-terminal α–α superhelix of Pat is required for mRNA decapping in metazoa
The EMBO Journal 29, 2368 (2010). doi:10.1038/emboj.2010.124
Authors: Joerg E Braun, Felix Tritschler, Gabrielle Haas, Cátia Igreja, Vincent Truffault, Oliver Weichenrieder & Elisa Izaurralde
Pat proteins regulate the transition of mRNAs from a state that is translationally active to one that is repressed, committing targeted mRNAs to degradation. Pat proteins contain a conserved N-terminal sequence, a proline-rich region, a Mid domain and a C-terminal domain (Pat-C). We show that
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Structural insights into the exquisite selectivity of neurexin/neuroligin synaptic interactions
Thu, 06/10/2010 - 23:00Structural insights into the exquisite selectivity of neurexin/neuroligin synaptic interactions
The EMBO Journal 29, 2461 (2010). doi:10.1038/emboj.2010.123
Authors: Philippe Leone, Davide Comoletti, Géraldine Ferracci, Sandrine Conrod, Simon U Garcia, Palmer Taylor, Yves Bourne & Pascale Marchot
The extracellular domains of neuroligins and neurexins interact through Ca2+ to form flexible trans-synaptic associations characterized by selectivity for neuroligin or neurexin subtypes. This heterophilic interaction, essential for synaptic maturation and differentiation, is regulated by gene selection, alternative mRNA splicing and post-translational
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