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EMBO Reports

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https://www.readbyqxmd.com/read/28642229/evolutionary-dynamics-of-the-kinetochore-network-in-eukaryotes-as-revealed-by-comparative-genomics
#1
Jolien Je van Hooff, Eelco Tromer, Leny M van Wijk, Berend Snel, Geert Jpl Kops
During eukaryotic cell division, the sister chromatids of duplicated chromosomes are pulled apart by microtubules, which connect via kinetochores. The kinetochore is a multiprotein structure that links centromeres to microtubules, and that emits molecular signals in order to safeguard the equal distribution of duplicated chromosomes over daughter cells. Although microtubule-mediated chromosome segregation is evolutionary conserved, kinetochore compositions seem to have diverged. To systematically inventory kinetochore diversity and to reconstruct its evolution, we determined orthologs of 70 kinetochore proteins in 90 phylogenetically diverse eukaryotes...
June 22, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28637682/cellular-mechanism-of-fibril-formation-from-serum-amyloid-a1-protein
#2
Stephanie Claus, Katrin Meinhardt, Tobias Aumüller, Ioana Puscalau-Girtu, Julia Linder, Christian Haupt, Paul Walther, Tatiana Syrovets, Thomas Simmet, Marcus Fändrich
Serum amyloid A1 (SAA1) is an apolipoprotein that binds to the high-density lipoprotein (HDL) fraction of the serum and constitutes the fibril precursor protein in systemic AA amyloidosis. We here show that HDL binding blocks fibril formation from soluble SAA1 protein, whereas internalization into mononuclear phagocytes leads to the formation of amyloid. SAA1 aggregation in the cell model disturbs the integrity of vesicular membranes and leads to lysosomal leakage and apoptotic death. The formed amyloid becomes deposited outside the cell where it can seed the fibrillation of extracellular SAA1...
June 21, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28630136/atp-synthase-complex-and-the-mitochondrial-permeability-transition-pore-poles-of-attraction
#3
Christos Chinopoulos
No abstract text is available yet for this article.
June 19, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28623189/the-anthropocene-neglects-misconceptions-and-possible-futures-the-term-anthropocene-is-often-erroneously-used-as-it-is-not-formally-defined-yet
#4
https://www.readbyqxmd.com/read/28623188/gli1-induced-deubiquitinase-usp48-aids-glioblastoma-tumorigenesis-by-stabilizing-gli1
#5
Aidong Zhou, Kangyu Lin, Sicong Zhang, Li Ma, Jianfei Xue, Saint-Aaron Morris, Kenneth D Aldape, Suyun Huang
Aberrant activation of the Hedgehog (Hh) signaling pathway drives the tumorigenesis of multiple cancers. In this study, we screened a panel of deubiquitinases that may regulate the Hh pathway. We find that deubiquitinase USP48 activates Gli-dependent transcription by stabilizing Gli1 protein. Mechanistically, USP48 interacts with Gli1 and cleaves its ubiquitin off directly. In glioblastoma cells, knockdown of USP48 inhibits cell proliferation and the expression of Gli1's downstream targets, which leads to repressed glioblastoma tumorigenesis...
June 16, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28623187/control-of-box-c-d-snornp-assembly-by-n-6-methylation-of-adenine
#6
Lin Huang, Saira Ashraf, Jia Wang, David Mj Lilley
N(6)-methyladenine is the most widespread mRNA modification. A subset of human box C/D snoRNA species have target GAC sequences that lead to formation of N(6)-methyladenine at a key trans Hoogsteen-sugar A·G base pair, of which half are methylated in vivo The GAC target is conserved only in those that are methylated. Methylation prevents binding of the 15.5-kDa protein and the induced folding of the RNA Thus, the assembly of the box C/D snoRNP could in principle be regulated by RNA methylation at its critical first stage...
June 16, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28615293/looping-out-mechanism-for-resolution-of-replicative-stress-at-telomeres
#7
Tianpeng Zhang, Zepeng Zhang, Feng Li, Qian Hu, Haiying Liu, Mengfan Tang, Wenbin Ma, Junjiu Huang, Zhou Songyang, Yikang Rong, Shichuan Zhang, Benjamin Pc Chen, Yong Zhao
Repetitive DNA is prone to replication fork stalling, which can lead to genome instability. Here, we find that replication fork stalling at telomeres leads to the formation of t-circle-tails, a new extrachromosomal structure that consists of circular telomeric DNA with a single-stranded tail. Structurally, the t-circle-tail resembles cyclized leading or lagging replication intermediates that are excised from the genome by topoisomerase II-mediated cleavage. We also show that the DNA damage repair machinery NHEJ is required for the formation of t-circle-tails and for the resolution of stalled replication forks, suggesting that NHEJ, which is normally constitutively suppressed at telomeres, is activated in the context of replication stress...
June 14, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28615292/rtt101-mms1-mms22-coordinates-replication-coupled-sister-chromatid-cohesion-and-nucleosome-assembly
#8
Jingjing Zhang, Di Shi, Xiaoli Li, Lin Ding, Jun Tang, Cong Liu, Katsuhiko Shirahige, Qinhong Cao, Huiqiang Lou
Two sister chromatids must be held together by a cohesion process from their synthesis during S phase to segregation in anaphase. Despite its pivotal role in accurate chromosome segregation, how cohesion is established remains elusive. Here, we demonstrate that yeast Rtt101-Mms1, Cul4 family E3 ubiquitin ligases are stronger dosage suppressors of loss-of-function eco1 mutants than PCNA The essential cohesion reaction, Eco1-catalyzed Smc3 acetylation is reduced in the absence of Rtt101-Mms1. One of the adaptor subunits, Mms22, associates directly with Eco1...
June 14, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28615291/high-affinity-cooperative-ca-2-binding-by-micu1-micu2-serves-as-an-on-off-switch-for-the%C3%A2-uniporter
#9
Kimberli J Kamer, Zenon Grabarek, Vamsi K Mootha
The mitochondrial calcium uniporter is a Ca(2+)-activated Ca(2+) channel that is essential for dynamic modulation of mitochondrial function in response to cellular Ca(2+) signals. It is regulated by two paralogous EF-hand proteins-MICU1 and MICU2, but the mechanism is unknown. Here, we demonstrate that both MICU1 and MICU2 are stabilized by Ca(2+) We reconstitute the MICU1-MICU2 heterodimer and demonstrate that it binds Ca(2+) cooperatively with high affinity. We discover that both MICU1 and MICU2 exhibit affinity for the mitochondria-specific lipid cardiolipin...
June 14, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28615290/a-post-translational-modification-switch-controls-coactivator-function-of-histone-methyltransferases-g9a-and-glp
#10
Coralie Poulard, Danielle Bittencourt, Dai-Ying Wu, Yixin Hu, Daniel S Gerke, Michael R Stallcup
Like many transcription regulators, histone methyltransferases G9a and G9a-like protein (GLP) can act gene-specifically as coregulators, but mechanisms controlling this specificity are mostly unknown. We show that adjacent post-translational methylation and phosphorylation regulate binding of G9a and GLP to heterochromatin protein 1 gamma (HP1γ), formation of a ternary complex with the glucocorticoid receptor (GR) on chromatin, and function of G9a and GLP as coactivators for a subset of GR target genes. HP1γ is recruited by G9a and GLP to GR binding sites associated with genes that require G9a, GLP, and HP1γ for glucocorticoid-stimulated transcription...
June 14, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28615289/enzyme-sub-functionalization-driven-by-regulation
#11
Bert van Loo, Erich Bornberg-Bauer
No abstract text is available yet for this article.
June 14, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28607035/murine-cytomegalovirus-ie3-dependent-transcription-is-required-for-dai-zbp1-mediated-necroptosis
#12
Haripriya Sridharan, Katherine B Ragan, Hongyan Guo, Ryan P Gilley, Vanessa J Landsteiner, William J Kaiser, Jason W Upton
DNA-dependent activator of interferon regulatory factors/Z-DNA binding protein 1 (DAI/ZBP1) is a crucial sensor of necroptotic cell death induced by murine cytomegalovirus (MCMV) in its natural host. Here, we show that viral capsid transport to the nucleus and subsequent viral IE3-dependent early transcription are required for necroptosis. Necroptosis induction does not depend on input virion DNA or newly synthesized viral DNA A putative RNA-binding domain of DAI/ZBP1, Zα2, is required to sense virus and trigger necroptosis...
June 12, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28607034/tctex-1-controls-ciliary-resorption-by-regulating-branched-actin-polymerization-and-endocytosis
#13
Masaki Saito, Wataru Otsu, Kuo-Shun Hsu, Jen-Zen Chuang, Teruyuki Yanagisawa, Vincent Shieh, Taku Kaitsuka, Fan-Yan Wei, Kazuhito Tomizawa, Ching-Hwa Sung
The primary cilium is a plasma membrane-protruding sensory organelle that undergoes regulated assembly and resorption. While the assembly process has been studied extensively, the cellular machinery that governs ciliary resorption is less well understood. Previous studies showed that the ciliary pocket membrane is an actin-rich, endocytosis-active periciliary subdomain. Furthermore, Tctex-1, originally identified as a cytoplasmic dynein light chain, has a dynein-independent role in ciliary resorption upon phosphorylation at Thr94...
June 12, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28607033/perception-of-root-active-cle-peptides-requires-coryne-function-in-the-phloem-vasculature
#14
Ora Hazak, Benjamin Brandt, Pietro Cattaneo, Julia Santiago, Antia Rodriguez-Villalon, Michael Hothorn, Christian S Hardtke
Arabidopsis root development is orchestrated by signaling pathways that consist of different CLAVATA3/EMBRYO SURROUNDING REGION (CLE) peptide ligands and their cognate CLAVATA (CLV) and BARELY ANY MERISTEM (BAM) receptors. How and where different CLE peptides trigger specific morphological or physiological changes in the root is poorly understood. Here, we report that the receptor-like protein CLAVATA 2 (CLV2) and the pseudokinase CORYNE (CRN) are necessary to fully sense root-active CLE peptides. We uncover BAM3 as the CLE45 receptor in the root and biochemically map its peptide binding surface...
June 12, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28600354/synergistic-action-of-auxin-and-cytokinin-mediates-aluminum-induced-root-growth-inhibition-in-arabidopsis
#15
Zhong-Bao Yang, Guangchao Liu, Jiajia Liu, Bing Zhang, Wenjing Meng, Bruno Müller, Ken-Ichiro Hayashi, Xiansheng Zhang, Zhong Zhao, Ive De Smet, Zhaojun Ding
Auxin acts synergistically with cytokinin to control the shoot stem-cell niche, while both hormones act antagonistically to maintain the root meristem. In aluminum (Al) stress-induced root growth inhibition, auxin plays an important role. However, the role of cytokinin in this process is not well understood. In this study, we show that cytokinin enhances root growth inhibition under stress by mediating Al-induced auxin signaling. Al stress triggers a local cytokinin response in the root-apex transition zone (TZ) that depends on IPTs, which encode adenosine phosphate isopentenyltransferases and regulate cytokinin biosynthesis...
June 9, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28588074/the-long-term-health-risks-of-art-epidemiological-data-and-research-on-animals-indicate-that-in-vitro-fertilization-might-create-health-problems-later-in-life
#16
https://www.readbyqxmd.com/read/28588073/brd4-brd2-isoform-switching-coordinates-pluripotent-exit-and-smad2-dependent-lineage-specification
#17
Rosalia Fernandez-Alonso, Lindsay Davidson, Jens Hukelmann, Michael Zengerle, Alan R Prescott, Angus Lamond, Alessio Ciulli, Gopal P Sapkota, Greg M Findlay
Pluripotent stem cells (PSCs) hold great clinical potential, as they possess the capacity to differentiate into fully specialised tissues such as pancreas, liver, neurons and cardiac muscle. However, the molecular mechanisms that coordinate pluripotent exit with lineage specification remain poorly understood. To address this question, we perform a small molecule screen to systematically identify novel regulators of the Smad2 signalling network, a key determinant of PSC fate. We reveal an essential function for BET family bromodomain proteins in Smad2 activation, distinct from the role of Brd4 in pluripotency maintenance...
June 6, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28588072/salt-inducible-kinase-induces-cytoplasmic-histone-deacetylase-4-to-promote-vascular-calcification
#18
Alon Abend, Omer Shkedi, Michal Fertouk, Lilac H Caspi, Izhak Kehat
A pathologic osteochondrogenic differentiation of vascular smooth muscle cells (VSMCs) promotes arterial calcifications, a process associated with significant morbidity and mortality. The molecular pathways promoting this pathology are not completely understood. We studied VSMCs, mouse aortic rings, and human aortic valves and showed here that histone deacetylase 4 (HDAC4) is upregulated early in the calcification process. Gain- and loss-of-function assays demonstrate that HDAC4 is a positive regulator driving this pathology...
June 6, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28588071/the-rna-helicase-dhx9-establishes-nucleolar-heterochromatin-and-this-activity-is-required-for-embryonic-stem-cell-differentiation
#19
Sergio Leone, Dominik Bär, Coenraad Frederik Slabber, Damian Dalcher, Raffaella Santoro
Long non-coding RNAs (lncRNAs) have been implicated in the regulation of chromatin conformation and epigenetic patterns. lncRNA expression levels are widely taken as an indicator for functional properties. However, the role of RNA processing in modulating distinct features of the same lncRNA is less understood. The establishment of heterochromatin at rRNA genes depends on the processing of IGS-rRNA into pRNA, a reaction that is impaired in embryonic stem cells (ESCs) and activated only upon differentiation...
June 6, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28566520/mitochondrial-permeability-transition-involves-dissociation-of-f1fo-atp-synthase-dimers-and-c-ring-conformation
#20
Massimo Bonora, Claudia Morganti, Giampaolo Morciano, Gaia Pedriali, Magdalena Lebiedzinska-Arciszewska, Giorgio Aquila, Carlotta Giorgi, Paola Rizzo, Gianluca Campo, Roberto Ferrari, Guido Kroemer, Mariusz R Wieckowski, Lorenzo Galluzzi, Paolo Pinton
The impact of the mitochondrial permeability transition (MPT) on cellular physiology is well characterized. In contrast, the composition and mode of action of the permeability transition pore complex (PTPC), the supramolecular entity that initiates MPT, remain to be elucidated. Specifically, the precise contribution of the mitochondrial F1FO ATP synthase (or subunits thereof) to MPT is a matter of debate. We demonstrate that F1FO ATP synthase dimers dissociate as the PTPC opens upon MPT induction. Stabilizing F1FO ATP synthase dimers by genetic approaches inhibits PTPC opening and MPT Specific mutations in the F1FO ATP synthase c subunit that alter C-ring conformation sensitize cells to MPT induction, which can be reverted by stabilizing F1FO ATP synthase dimers...
May 31, 2017: EMBO Reports
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