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https://www.readbyqxmd.com/read/28733325/protease-cleavage-site-fingerprinting-by-label-free-in-gel-degradomics-reveals-ph-dependent-specificity-switch-of-legumain
#1
Robert Vidmar, Matej Vizovišek, Dušan Turk, Boris Turk, Marko Fonović
Determination of protease specificity is of crucial importance for understanding protease function. We have developed the first gel-based label-free proteomic approach (DIPPS-direct in-gel profiling of protease specificity) that enables quick and reliable determination of protease cleavage specificities under large variety of experimental conditions. The methodology is based on in-gel digestion of the gel-separated proteome with the studied protease, enrichment of cleaved peptides by gel extraction, and subsequent mass spectrometry analysis combined with a length-limited unspecific database search...
July 21, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28729434/cohesins-and-condensins-orchestrate-the-4d-dynamics-of-yeast-chromosomes-during-the-cell%C3%A2-cycle
#2
Luciana Lazar-Stefanita, Vittore F Scolari, Guillaume Mercy, Héloise Muller, Thomas M Guérin, Agnès Thierry, Julien Mozziconacci, Romain Koszul
Duplication and segregation of chromosomes involves dynamic reorganization of their internal structure by conserved architectural proteins, including the structural maintenance of chromosomes (SMC) complexes cohesin and condensin. Despite active investigation of the roles of these factors, a genome-wide view of dynamic chromosome architecture at both small and large scale during cell division is still missing. Here, we report the first comprehensive 4D analysis of the higher-order organization of the Saccharomyces cerevisiae genome throughout the cell cycle and investigate the roles of SMC complexes in controlling structural transitions...
July 20, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28724529/coactivators-and-general-transcription-factors-have-two-distinct-dynamic-populations-dependent-on%C3%A2-transcription
#3
Nikolaos Vosnakis, Marc Koch, Elisabeth Scheer, Pascal Kessler, Yves Mély, Pascal Didier, László Tora
SAGA and ATAC are two distinct chromatin modifying co-activator complexes with distinct enzymatic activities involved in RNA polymerase II (Pol II) transcription regulation. To investigate the mobility of co-activator complexes and general transcription factors in live-cell nuclei, we performed imaging experiments based on photobleaching. SAGA and ATAC, but also two general transcription factors (TFIID and TFIIB), were highly dynamic, exhibiting mainly transient associations with chromatin, contrary to Pol II, which formed more stable chromatin interactions...
July 19, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28724528/a-forceful-connection-mechanoregulation-of-oncogenic-yap
#4
Ralph Thomas Böttcher, Zhiqi Sun, Reinhard Fässler
No abstract text is available yet for this article.
July 19, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28716805/sensing-of-viral-and-endogenous-rna-by-zbp1-dai-induces-necroptosis
#5
Jonathan Maelfait, Layal Liverpool, Anne Bridgeman, Katherine B Ragan, Jason W Upton, Jan Rehwinkel
Nucleic acids are potent triggers for innate immunity. Double-stranded DNA and RNA adopt different helical conformations, including the unusual Z-conformation. Z-DNA/RNA is recognised by Z-binding domains (ZBDs), which are present in proteins implicated in antiviral immunity. These include ZBP1 (also known as DAI or DLM-1), which induces necroptosis, an inflammatory form of cell death. Using reconstitution and knock-in models, we report that mutation of key amino acids involved in Z-DNA/RNA binding in ZBP1's ZBDs prevented necroptosis upon infection with mouse cytomegalovirus...
July 17, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28716804/type-i-interferon-is-required-for-t-helper-th-2-induction-by-dendritic-cells
#6
Lauren M Webb, Rachel J Lundie, Jessica G Borger, Sheila L Brown, Lisa M Connor, Adam Nr Cartwright, Annette M Dougall, Ruud Hp Wilbers, Peter C Cook, Lucy H Jackson-Jones, Alexander T Phythian-Adams, Cecilia Johansson, Daniel M Davis, Benjamin G Dewals, Franca Ronchese, Andrew S MacDonald
Type 2 inflammation is a defining feature of infection with parasitic worms (helminths), as well as being responsible for widespread suffering in allergies. However, the precise mechanisms involved in T helper (Th) 2 polarization by dendritic cells (DCs) are currently unclear. We have identified a previously unrecognized role for type I IFN (IFN-I) in enabling this process. An IFN-I signature was evident in DCs responding to the helminth Schistosoma mansoni or the allergen house dust mite (HDM). Further, IFN-I signaling was required for optimal DC phenotypic activation in response to helminth antigen (Ag), and efficient migration to, and localization with, T cells in the draining lymph node (dLN)...
July 17, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28710261/the-lipid-binding-side-of-notch-ligands
#7
Ben-Zion Shilo, David Sprinzak
No abstract text is available yet for this article.
July 14, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28701485/gt-rich-promoters-can-drive-rna-pol-ii-transcription-and-deposition-of-h2a-z-in-african-trypanosomes
#8
Carolin Wedel, Konrad U Förstner, Ramona Derr, T Nicolai Siegel
Genome-wide transcription studies are revealing an increasing number of "dispersed promoters" that, unlike "focused promoters", lack well-conserved sequence motifs and tight regulation. Dispersed promoters are nevertheless marked by well-defined chromatin structures, suggesting that specific sequence elements must exist in these unregulated promoters. Here, we have analyzed regions of transcription initiation in the eukaryotic parasite Trypanosoma brucei, in which RNA polymerase II transcription initiation occurs over broad regions without distinct promoter motifs and lacks regulation...
July 12, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28701484/sirt1-regulates-macrophage-self-renewal
#9
Francesco Imperatore, Julien Maurizio, Stephanie Vargas Aguilar, Clara J Busch, Jérémy Favret, Elisabeth Kowenz-Leutz, Wilfried Cathou, Rebecca Gentek, Pierre Perrin, Achim Leutz, Carole Berruyer, Michael H Sieweke
Mature differentiated macrophages can self-maintain by local proliferation in tissues and can be extensively expanded in culture under specific conditions, but the mechanisms of this phenomenon remain only partially defined. Here, we show that SIRT1, an evolutionary conserved regulator of life span, positively affects macrophage self-renewal ability in vitro and in vivo Overexpression of SIRT1 during bone marrow-derived macrophage differentiation increased their proliferative capacity. Conversely, decrease of SIRT1 expression by shRNA inactivation, CRISPR/Cas9 mediated deletion and pharmacological inhibition restricted macrophage self-renewal in culture...
July 12, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28701483/the-shigella-type-iii-effector-ipgd-recodes-ca-2-signals-during-invasion-of-epithelial-cells
#10
Chun Hui Sun, Benjamin Wacquier, Daniel I Aguilar, Nathalie Carayol, Kevin Denis, Sylviane Boucherie, Cesar Valencia-Gallardo, Ceren Simsek, Christophe Erneux, Alexandre Lehman, Jost Enninga, Laurence Arbibe, Philippe Sansonetti, Geneviève Dupont, Laurent Combettes, Guy Tran Van Nhieu
The role of second messengers in the diversion of cellular processes by pathogens remains poorly studied despite their importance. Among these, Ca(2+) virtually regulates all known cell processes, including cytoskeletal reorganization, inflammation, or cell death pathways. Under physiological conditions, cytosolic Ca(2+) increases are transient and oscillatory, defining the so-called Ca(2+) code that links cell responses to specific Ca(2+) oscillatory patterns. During cell invasion, Shigella induces atypical local and global Ca(2+) signals...
July 12, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28694245/fundamental-cell-cycle-kinases-collaborate-to-ensure-timely-destruction-of-the-synaptonemal-complex-during-meiosis
#11
Bilge Argunhan, Wing-Kit Leung, Negar Afshar, Yaroslav Terentyev, Vijayalakshmi V Subramanian, Yasuto Murayama, Andreas Hochwagen, Hiroshi Iwasaki, Tomomi Tsubouchi, Hideo Tsubouchi
The synaptonemal complex (SC) is a proteinaceous macromolecular assembly that forms during meiotic prophase I and mediates adhesion of paired homologous chromosomes along their entire lengths. Although prompt disassembly of the SC during exit from prophase I is a landmark event of meiosis, the underlying mechanism regulating SC destruction has remained elusive. Here, we show that DDK (Dbf4-dependent Cdc7 kinase) is central to SC destruction. Upon exit from prophase I, Dbf4, the regulatory subunit of DDK, directly associates with and is phosphorylated by the Polo-like kinase Cdc5...
July 10, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28694244/tumor-matrix-stiffness-promotes-metastatic-cancer-cell-interaction-with-the-endothelium
#12
Steven E Reid, Emily J Kay, Lisa J Neilson, Anne-Theres Henze, Jens Serneels, Ewan J McGhee, Sandeep Dhayade, Colin Nixon, John Bg Mackey, Alice Santi, Karthic Swaminathan, Dimitris Athineos, Vasileios Papalazarou, Francesca Patella, Álvaro Román-Fernández, Yasmin ElMaghloob, Juan Ramon Hernandez-Fernaud, Ralf H Adams, Shehab Ismail, David M Bryant, Manuel Salmeron-Sanchez, Laura M Machesky, Leo M Carlin, Karen Blyth, Massimiliano Mazzone, Sara Zanivan
Tumor progression alters the composition and physical properties of the extracellular matrix. Particularly, increased matrix stiffness has profound effects on tumor growth and metastasis. While endothelial cells are key players in cancer progression, the influence of tumor stiffness on the endothelium and the impact on metastasis is unknown. Through quantitative mass spectrometry, we find that the matricellular protein CCN1/CYR61 is highly regulated by stiffness in endothelial cells. We show that stiffness-induced CCN1 activates β-catenin nuclear translocation and signaling and that this contributes to upregulate N-cadherin levels on the surface of the endothelium, in vitro This facilitates N-cadherin-dependent cancer cell-endothelium interaction...
July 10, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28694243/expanding-our-scientific-horizons-utilization-of-unique-model-organisms-in-biological-research
#13
Angela K Peter, Claudia Crocini, Leslie A Leinwand
No abstract text is available yet for this article.
July 10, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28694242/chromatin-stiffening-underlies-enhanced-locus-mobility-after-dna-damage-in-budding-yeast
#14
Sébastien Herbert, Alice Brion, Jean-Michel Arbona, Mickaël Lelek, Adeline Veillet, Benoît Lelandais, Jyotsana Parmar, Fabiola García Fernández, Etienne Almayrac, Yasmine Khalil, Eleonore Birgy, Emmanuelle Fabre, Christophe Zimmer
DNA double-strand breaks (DSBs) induce a cellular response that involves histone modifications and chromatin remodeling at the damaged site and increases chromosome dynamics both locally at the damaged site and globally in the nucleus. In parallel, it has become clear that the spatial organization and dynamics of chromosomes can be largely explained by the statistical properties of tethered, but randomly moving, polymer chains, characterized mainly by their rigidity and compaction. How these properties of chromatin are affected during DNA damage remains, however, unclear...
July 10, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28684539/ppr-polyadenylation-factor-defines-mitochondrial-mrna-identity-and-stability-in-trypanosomes
#15
Liye Zhang, Francois M Sement, Takuma Suematsu, Tian Yu, Stefano Monti, Lan Huang, Ruslan Aphasizhev, Inna Aphasizheva
In Trypanosoma brucei, most mitochondrial mRNAs undergo internal changes by RNA editing and 3' end modifications. The temporally separated and functionally distinct modifications are manifested by adenylation prior to editing, and by post-editing extension of a short A-tail into a long A/U-heteropolymer. The A-tail stabilizes partially and fully edited mRNAs, while the A/U-tail enables mRNA binding to the ribosome. Here, we identify an essential pentatricopeptide repeat-containing RNA binding protein, kinetoplast polyadenylation factor 3 (KPAF3), and demonstrate its role in protecting pre-mRNA against degradation by the processome...
July 6, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28679504/mitochondrial-genome-inheritance-and-replacement-in-the-human-germline
#16
Don P Wolf, Tomonari Hayama, Shoukhrat Mitalipov
Mitochondria, the ubiquitous power packs in nearly every eukaryotic cell, contain their own DNA, known as mtDNA, which is inherited exclusively from the mother. The number of mitochondrial genomes varies depending on the cell's energy needs. The mature oocyte contains the highest number of mitochondria of any cell type, although there is little if any mtDNA replication after fertilization until the embryo implants. This has potential repercussions for mitochondrial replacement therapy (MRT; see description of currently employed methods below) used to prevent the transmission of mtDNA-based disorders...
July 5, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28673932/integrin-%C3%AE-v%C3%AE-3-enhances-the-suppressive-effect-of-interferon-%C3%AE-on-hematopoietic-stem-cells
#17
Terumasa Umemoto, Yu Matsuzaki, Yoshiko Shiratsuchi, Michihiro Hashimoto, Takayuki Yoshimoto, Ayako Nakamura-Ishizu, Brian Petrich, Masayuki Yamato, Toshio Suda
Hematopoietic homeostasis depends on the maintenance of hematopoietic stem cells (HSCs), which are regulated within a specialized bone marrow (BM) niche. When HSC sense external stimuli, their adhesion status may be critical for determining HSC cell fate. The cell surface molecule, integrin αvβ3, is activated through HSC adhesion to extracellular matrix and niche cells. Integrin β3 signaling maintains HSCs within the niche. Here, we showed the synergistic negative regulation of the pro-inflammatory cytokine interferon-γ (IFNγ) and β3 integrin signaling in murine HSC function by a novel definitive phenotyping of HSCs...
July 3, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28673931/mechanical-cue-induced-yap-instructs-skp2-dependent-cell-cycle-exit-and-oncogenic-signaling
#18
Wonyul Jang, Tackhoon Kim, Ja Seung Koo, Sang-Kyum Kim, Dae-Sik Lim
Mechanical tensions are usually generated during development at spatially defined regions within tissues. Such physical cues dictate the cellular decisions of proliferation or cell cycle arrest. Yet, the mechanisms by which mechanical stress controls the cell cycle are not yet fully understood. Here, we report that mechanical cues function upstream of Skp2 transcription in human breast cancer cells. We found that YAP, the mechano-responsive oncogenic Hippo signaling effector, directly promotes Skp2 transcription...
July 3, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28666995/structural-basis-of-divergent-cyclin-dependent-kinase-activation-by-spy1-ringo-proteins
#19
Denise A McGrath, Bre-Anne Fifield, Aimee H Marceau, Sarvind Tripathi, Lisa A Porter, Seth M Rubin
Cyclin-dependent kinases (Cdks) are principal drivers of cell division and are an important therapeutic target to inhibit aberrant proliferation. Cdk enzymatic activity is tightly controlled through cyclin interactions, posttranslational modifications, and binding of inhibitors such as the p27 tumor suppressor protein. Spy1/RINGO (Spy1) proteins bind and activate Cdk but are resistant to canonical regulatory mechanisms that establish cell-cycle checkpoints. Cancer cells exploit Spy1 to stimulate proliferation through inappropriate activation of Cdks, yet the mechanism is unknown...
June 30, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28666994/a-chief-source-of-cancer-and-repair-in-stomachs
#20
Megan D Radyk, Jason C Mills
No abstract text is available yet for this article.
June 30, 2017: EMBO Journal
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