EMBO Reports

The psycho gene.

Publication Date: 2010 Sep PMID: 20805840
Authors: Hunter, P.
Journal: EMBO Rep

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B for bureaucracy.

Publication Date: 2010 Sep PMID: 20805839
Authors: Wolinsky, H.
Journal: EMBO Rep

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Dynein at the nuclear envelope.

Publication Date: 2010 Sep PMID: 20805838
Authors: Tanenbaum, M. E. - Akhmanova, A. - Medema, R. H.
Journal: EMBO Rep

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Managing academic research.

Publication Date: 2010 Sep PMID: 20805837
Authors: van Helden, P.
Journal: EMBO Rep

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Anarchy for the EMBC.

Publication Date: 2010 Sep PMID: 20805836
Authors: Jacobs, H.
Journal: EMBO Rep

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Dop functions as a depupylase in the prokaryotic ubiquitin-like modification pathway.

Publication Date: 2010 Aug 27 PMID: 20798673
Authors: Imkamp, F. - Striebel, F. - Sutter, M. - Ozcelik, D. - Zimmermann, N. - Sander, P. - Weber-Ban, E.
Journal: EMBO Rep

Post-translational modification of proteins with prokaryotic ubiquitin-like protein (Pup) is the bacterial equivalent of ubiquitination in eukaryotes. Mycobacterial pupylation is a two-step process in which the carboxy-terminal glutamine of Pup is first deamidated by Dop (deamidase of Pup) before ligation of the generated gamma-carboxylate to substrate lysines by the Pup ligase PafA. In this study, we identify a new feature of the pupylation system by demonstrating that Dop also acts as a depupylase in the Pup proteasome system in vivo and in vitro. Dop removes Pup from substrates by specific cleavage of the isopeptide bond. Depupylation can be enhanced by the unfolding activity of the mycobacterial proteasomal ATPase Mpa.

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Mitochondrial shape changes: orchestrating cell pathophysiology.

Publication Date: 2010 Sep PMID: 20725092
Authors: Campello, S. - Scorrano, L.
Journal: EMBO Rep

Mitochondria are highly dynamic organelles, the location, size and distribution of which are controlled by a family of proteins that modulate mitochondrial fusion and fission. Recent evidence indicates that mitochondrial morphology is crucial for cell physiology, as changes in mitochondrial shape have been linked to neurodegeneration, calcium signalling, lifespan and cell death. Because immune cells contain few mitochondria, these organelles have been considered to have only a marginal role in this physiological context-which is conversely well characterized from the point of view of signalling. Nevertheless, accumulating evidence shows that mitochondrial dynamics have an impact on the migration and activation of immune cells and on the innate immune response. Here, we discuss the roles of mitochondrial dynamics in cell pathophysiology and consider how studying dynamics in the context of the immune system could increase our knowledge about the role of dynamics in key signalling cascades.

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A voice for science in Europe.

Publication Date: 2010 Sep PMID: 20725091
Authors:
Journal: EMBO Rep

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Understanding human genetic variation in the era of high-throughput sequencing.

Publication Date: 2010 Sep PMID: 20725090
Authors: Knight, J. C.
Journal: EMBO Rep

The EMBO/EMBL symposium 'Human Variation: Cause and Consequence' highlighted advances in understanding the molecular basis of human genetic variation and its myriad implications for biology, human origins and disease. As high-throughput sequencing allows us to define genetic variation and its functional consequences at genome-wide resolution for a large number of people, important questions need to be asked about how to use new technologies to maximize the translational relevance of genetic research for society and the individual patient.

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An eruption of European B-cell biology.

Publication Date: 2010 Sep PMID: 20725089
Authors: Cancro, M. P.
Journal: EMBO Rep

Volcanic ash clouds disrupted the 2010 ESF/EMBO meeting on B cells and protection. Nevertheless, the delegates who did make it to Catalonia put together their own programme of talks covering a range of themes from mutualism to epigenetics.

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Structural insight into the oxidation-sensing mechanism of the antibiotic resistance of regulator MexR.

Publication Date: 2010 Sep PMID: 20706222
Authors: Chen, H. - Yi, C. - Zhang, J. - Zhang, W. - Ge, Z. - Yang, C. G. - He, C.
Journal: EMBO Rep

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Histone Sin mutations promote nucleosome traversal and histone displacement by RNA polymerase II.

Publication Date: 2010 Sep PMID: 20706221
Authors: Hsieh, F. K. - Fisher, M. - Ujvari, A. - Studitsky, V. M. - Luse, D. S.
Journal: EMBO Rep

Nucleosome traversal by RNA polymerase II (pol II) and recovery of chromatin structure after transcription are essential for proper gene expression. In this paper we show that nucleosomes assembled with Sin mutant histones present a much weaker barrier to traversal by pol II and are less likely to survive transcription. Increases in traversal from incorporation of Sin mutant histones and histones lacking H2A/H2B amino-terminal tails were in most cases additive, indicating that traversal can be facilitated by distinct mechanisms. We had identified a key intermediate in traversal, the zero (slashed circle)-loop, which mediates nucleosome survival during transcription. Sin mutations probably destabilize these intermediates and thus increase the likelihood of nucleosome disassociation.

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Who needs a greener revolution?

Publication Date: 2010 Sep PMID: 20706220
Authors: Rull, V.
Journal: EMBO Rep

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The ZEB/miR-200 feedback loop-a motor of cellular plasticity in development and cancer?

Publication Date: 2010 Sep PMID: 20706219
Authors: Brabletz, S. - Brabletz, T.
Journal: EMBO Rep

Epithelial-to-mesenchymal transition (EMT) is a fundamental process in development and disease. Zinc-finger enhancer binding (ZEB) transcription factors (ZEB1 and ZEB2) are crucial EMT activators, whereas members of the miR-200 family induce epithelial differentiation. They are reciprocally linked in a feedback loop, each strictly controlling the expression of the other. Now data show that EMT not only confers cellular motility, but also induces stem-cell properties and prevents apoptosis and senescence. Thus the balanced expression of ZEB factors and miR-200 controls all these processes. We therefore propose that the ZEB/miR-200 feedback loop is the molecular motor of cellular plasticity in development and disease, and in particular is a driving force for cancer progression towards metastasis by controlling the state of cancer stem cells.

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Nucleotide supply, not local histone acetylation, sets replication origin usage in transcribed regions.

Publication Date: 2010 Sep PMID: 20671737
Authors: Gay, S. - Lachages, A. M. - Millot, G. A. - Courbet, S. - Letessier, A. - Debatisse, M. - Brison, O.
Journal: EMBO Rep

In eukaryotes, only a fraction of replication origins fire at each S phase. Local histone acetylation was proposed to control firing efficiency of origins, but conflicting results were obtained. We report that local histone acetylation does not reflect origin efficiencies along the adenosine monophosphate deaminase 2 locus in mammalian fibroblasts. Reciprocally, modulation of origin efficiency does not affect acetylation. However, treatment with a deacetylase inhibitor changes the initiation pattern. We demonstrate that this treatment alters pyrimidine biosynthesis and decreases fork speed, which recruits latent origins. Our findings reconcile results that seemed inconsistent and reveal an unsuspected effect of deacetylase inhibitors on replication dynamics.

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Intronic hammerhead ribozymes are ultraconserved in the human genome.

Publication Date: 2010 Sep PMID: 20651741
Authors: de la Pena, M. - Garcia-Robles, I.
Journal: EMBO Rep

Small ribozymes have been regarded as living fossils of a prebiotic RNA world that would have remained in the genomes of modern organisms. In this study, we report the ultraconserved occurrence of hammerhead ribozymes in Amniota genomes (reptiles, birds and mammals, including humans), similar to those described previously in amphibians and platyhelminth parasites. The ribozymes mapped to intronic regions of different genes, such as the tumour suppressor RECK in birds and mammals, a mammalian tumour antigen and the dystrobrevin beta in lizards and birds. In vitro characterization confirmed a high self-cleavage activity, whereas analysis of RECK-expressed sequence tags revealed fusion events between the in vivo self-cleaved intron and U5 or U6 small nuclear RNA fragments. Together, these results suggest a conserved role for these ribozymes in messenger RNA biogenesis.

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Acetylation-dependent oncogenic activity of metastasis-associated protein 1 co-regulator.

Publication Date: 2010 Sep PMID: 20651739
Authors: Ohshiro, K. - Rayala, S. K. - Wigerup, C. - Pakala, S. B. - Natha, R. S. - Gururaj, A. E. - Molli, P. R. - Mansson, S. S. - Ramezani, A. - Hawley, R. G. - Landberg, G. - Lee, N. H. - Kumar, R.
Journal: EMBO Rep

High expression of metastasis-associated protein 1 co-regulator (MTA1), a component of the nuclear remodelling and histone deacetylase complex, has been associated with human tumours. However, the precise role of MTA1 in tumorigenesis remains unknown. In this study, we show that induced levels of MTA1 are sufficient to transform Rat1 fibroblasts and that the transforming potential of MTA1 is dependent on its acetylation at Lys626. Underlying mechanisms of MTA1-mediated transformation include activation of the Ras-Raf pathway by MTA1 but not by acetylation-inactive MTA1; this was due to the repression of Galphai2 transcription, which negatively influences Ras activation. We observed that acetylated MTA1-histone deacetylase (HDAC) interaction was required for the recruitment of the MTA1-HDAC complex to the Galphai2 regulatory element and consequently for the repression of Galphai2 transcription and expression leading to activation of the Ras-Raf pathway. The findings presented in this study provide for the first time-to the best of our knowledge-evidence of acetylation-dependent oncogenic activity of a cancer-relevant gene product.

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Structural insight into the oxidation-sensing mechanism of the antibiotic resistance of regulator MexR.

Publication Date: 2010 Sep PMID: 20616806
Authors: Chen, H. - Yi, C. - Zhang, J. - Zhang, W. - Ge, Z. - Yang, C. G. - He, C.
Journal: EMBO Rep

MexR functions as the primary regulator of the mexAB-oprM multidrug efflux expression in Pseudomonas aeruginosa. It has been shown that MexR senses oxidative stress by interprotomer disulphide bond formation between redox-active cysteines. This oxidation induces MexR to dissociate from the promoter DNA, thus activating the transcriptional expression of efflux pump genes. In this study, we present the crystal structure of MexR in its oxidized form at a resolution of 2.1 A. This crystal structure reveals the mechanism by which oxidative signal allosterically derepresses the MexR-controlled transcription activation.

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