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| Open AccessSelective inhibition of microRNA accessibility by RBM38 is required for p53 activity
MicroRNAs bind to the 3′-untranslated region of genes to regulate expression. In this study, an RNA-binding protein, RMB38, is shown to selectively regulate the access of some microRNAs to their targets, and control the expression of some p53 target genes.
- Nicolas Léveillé
- , Ran Elkon
- & Reuven Agami
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A chloroplast envelope-bound PHD transcription factor mediates chloroplast signals to the nucleus
Retrograde chloroplast signals are essential in coordinating nuclear gene expression, but the mechanism that relays chloroplast signals to the nucleus remains elusive. In this study, a chloroplast envelope-bound transcription factor PTM is shown to transmit chloroplast signals to the nucleus.
- Xuwu Sun
- , Peiqiang Feng
- & Lixin Zhang
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Article
| Open AccessA CLASP-modulated cell edge barrier mechanism drives cell-wide cortical microtubule organization in Arabidopsis
How microtubules are organized correctly in plant cells is not well understood. Ambroseet al. use 4D imaging and computer modelling to show that sharp cell edges induce microtubule depolymerization and that the microtubule-associated protein CLASP mitigates this process to modulate array organization.
- Chris Ambrose
- , Jun F. Allard
- & Geoffrey O. Wasteneys
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Article
| Open AccessArabidopsis nitrate reductase activity is stimulated by the E3 SUMO ligase AtSIZ1
Posttranslational modification of proteins by small ubiquitin-related modifier is a response to stress signalling in plants. Here, theArabdiposisprotein SIZ1 is shown to cause SUMOylation of nitrate reductases 1 and 2 and to increase their activity, suggesting that SIZ1 controls nitrate uptake via SUMOylation.
- Bong Soo Park
- , Jong Tae Song
- & Hak Soo Seo
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Identification of the PGRMC1 protein complex as the putative sigma-2 receptor binding site
The sigma-2 receptor is used as a biomarker for tumour cell proliferation but its identity is unknown. Using a novel radiolabelled probe, the authors identify progesterone receptor membrane component 1, which is overexpressed in several tumour types, as the putative sigma-2 receptor.
- Jinbin Xu
- , Chenbo Zeng
- & Robert H. Mach
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Cyclin B-dependent kinase 1 regulates human TRF1 to modulate the resolution of sister telomeres
TRF1 is a telomere binding protein involved in sister telomere cohesion. In this study, the ability of TRF1 to bind to telomeres in mitosis is inhibited by cyclin-dependent kinase 1-mediated phosphorylation, which may facilitate sister telomere resolution during mitosis.
- Megan McKerlie
- & Xu-Dong Zhu
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Article
| Open AccessTRAF6 ubiquitinates TGFβ type I receptor to promote its cleavage and nuclear translocation in cancer
TGFβ can function as both a tumour suppressor and tumour promoter under different cellular contexts. Here, the cleavage product of the TGFβ type I receptor is shown to be generated in a TGFβ-dependent manner, and can induce the expression of genes involved in tumour cell invasion.
- Yabing Mu
- , Reshma Sundar
- & Marene Landström
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Article
| Open AccessStructure and Scm3-mediated assembly of budding yeast centromeric nucleosomes
There is debate about the structural organization of the yeast centromeric nucleosome and the role of the nonhistone protein Scm3 in its assembly. Dechassaet al.find that yeast centromeric nucleosomes organize DNA in a left-handed superhelix, and show that Scm3 is a specific nucleosome assembly factor.
- Mekonnen Lemma Dechassa
- , Katharina Wyns
- & Karolin Luger
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Article
| Open AccessTranscription factor IRF8 directs a silencing programme for TH17 cell differentiation
The molecular mechanisms that regulate TH17 cell diversity are poorly understood. Ouyang et al. show that the transcription factor interferon regulatory factor-8 is required for TH17-cell differentiation and that its absence increases the severity of an experimental model of colitis.
- Xinshou Ouyang
- , Ruihua Zhang
- & Huabao Xiong
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Article
| Open AccessIKKβ regulates essential functions of the vascular endothelium through kinase-dependent and -independent pathways
IKK kinases activate nuclear factor-κB, and the activated form of this transcription factor is found in endothelial cells in diseased tissue. In this study, mice lacking IKKβ in the endothelium are generated, and it is shown that defects in endothelial cell function are both IKK kinase activity dependent and independent.
- Noboru Ashida
- , Sucharita SenBanerjee
- & Anthony Rosenzweig
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Article
| Open AccessAurora B potentiates Mps1 activation to ensure rapid checkpoint establishment at the onset of mitosis
Mitotic exit is controlled by a cell division checkpoint that prevents premature degradation of cyclin B by the anaphase-promoting complex. Saurinet al. show that Aurora B directly regulates timely establishment of this checkpoint by facilitating activation of Mps1 kinase at unattached kinetochores.
- Adrian T. Saurin
- , Maike S. van der Waal
- & Geert J.P.L. Kops
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Article
| Open AccessChemical treatment enhances skipping of a mutated exon in the dystrophin gene
Duchenne muscular dystrophy is caused by a loss of thedystrophin gene, and control of dystrophin mRNA splicing could aid treatment of the disease. Nishida et al. show that a small molecule promotes skipping of exon 31 and increases production of a functional dystrophin protein in a patient.
- Atsushi Nishida
- , Naoyuki Kataoka
- & Masafumi Matsuo
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Two splice variants of the IDD14 transcription factor competitively form nonfunctional heterodimers which may regulate starch metabolism
The alternative splicing of genes increases the number and diversity of proteins produced within a cell. Seoet al. demonstrate that the beta form of the alternatively spliced Arabidopsis gene, IDD14, is produced under cold conditions and may have a role in regulating starch accumulation.
- Pil Joon Seo
- , Mi Jung Kim
- & Chung-Mo Park
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Mutual adaptation of a membrane protein and its lipid bilayer during conformational changes
The detailed interactions of membrane proteins with their lipid environment are poorly understood. Sonntaget al. use low-resolution X-ray crystallographic data and molecular dynamics simulations to study the manner in which the sarcoendoplasmic reticulum Ca2+–ATPase adapts to different membrane environments.
- Yonathan Sonntag
- , Maria Musgaard
- & Lea Thøgersen
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α-Mannosidase 2C1 attenuates PTEN function in prostate cancer cells
PTEN is a phosphatase that regulates the phosphatidylinositol-3 kinase signalling pathway and is inactivated in many tumour types. Heet al.show that a mannosidase, α-mannosidase 2C1, can inactivate PTEN in prostate cancer cells, and that PTEN-positive human prostate tumours overexpress α-mannosidase 2C1.
- Lizhi He
- , Catherine Fan
- & Damu Tang
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LTD is a protein required for sorting light-harvesting chlorophyll-binding proteins to the chloroplast SRP pathway
Chloroplast proteins are synthesized in the cytosol and imported into the chloroplast before being delivered to the thylakoids. The authors report that an ankyrin-repeat protein, LTD, is essential for the routing of chlorophyll-binding proteins to the signal recognition particle pathway.
- Min Ouyang
- , Xiaoyi Li
- & Lixin Zhang
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Article
| Open AccessAnnexin-A5 assembled into two-dimensional arrays promotes cell membrane repair
Eukaryotic cell plasma membranes possess a mechanism to repair tears caused by stimuli such as mechanical stress. The authors demonstrate that annexin-A5, when assembled into two-dimensional arrays in the presence of calcium, is required for membrane repair.
- Anthony Bouter
- , Céline Gounou
- & Alain R. Brisson
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Adhesive water networks facilitate binding of protein interfaces
The formation of hydrophilic protein–protein interactions cannot be explained by charge–charge interactions. Here, molecular simulations reveal that water forms an adhesive hydrogen-bonded network between proteins, stabilizing intermediate states before the bound complex forms.
- Mazen Ahmad
- , Wei Gu
- & Volkhard Helms
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The acetylation of tau inhibits its function and promotes pathological tau aggregation
Phosphorylation of the microtubule-associated protein tau is associated with disease, but other post-translational modifications of tau are not well studied. Here, Cohenet al. study the acetylation of tau and suggest that this form of the protein may be associated with tauopathies.
- Todd J. Cohen
- , Jing L. Guo
- & Virginia M. Y. Lee
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Article
| Open AccessThe structural basis for selective binding of non-methylated CpG islands by the CFP1 CXXC domain
CXXC domain proteins bind to CpG DNA sequences and influence chromatin modification. Xuet al.report crystal structures of the CXXC protein CFP1, a component of the SETD1 histone H3K4 methyl transferase complex, and study the molecular mechanisms of DNA-binding specificity.
- Chao Xu
- , Chuanbing Bian
- & Jinrong Min
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Article
| Open AccessStructural basis for the recognition and cleavage of histone H3 by cathepsin L
Cathepsin L mediates proteolysis of the histone H3 tail and is a factor in cell-cycle progression and cellular differentiation. Adams-Cioabaet al. report crystal structures of an inactive mutant of the protease complexed with substrate peptides, and find that it is highly accommodating of modified substrates.
- Melanie A. Adams-Cioaba
- , Joanne C. Krupa
- & Jinrong Min
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Rad23 escapes degradation because it lacks a proteasome initiation region
Rad23 accompanies ubiquitinated substrates to the proteasome for destruction but manages to avoid degradation. In this study, Fishbainet al.show that Rad23 escapes because it lacks an effective initiation region; therefore, the proteasome is unable to engage the protein and unfold it.
- Susan Fishbain
- , Sumit Prakash
- & Andreas Matouschek
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Article
| Open AccessC-terminal UBA domains protect ubiquitin receptors by preventing initiation of protein degradation
Rad23 and Dsk2 bind polyubiquitylated proteins and escort them to the proteasome for destruction. In this study, Heinenet al.investigate the molecular mechanisms that protect the C-terminal UBA domains of Rad23 and Dsk2 from proteasomal destruction.
- Christian Heinen
- , Klàra Ács
- & Nico P. Dantuma
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Article
| Open AccessStretching fibronectin fibres disrupts binding of bacterial adhesins by physically destroying an epitope
Bacteria express adhesive proteins on their surface that recognize fibronectin. Using a mechanical stretch assay and steered molecular dynamics, Chabriaet al. demonstrate that the binding of a bacterial adhesin to fibronectin is mechanoregulated, suggesting that bacteria can sense tissue fibre stretching.
- Mamta Chabria
- , Samuel Hertig
- & Viola Vogel
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Article
| Open AccessDisruption of TBP-2 ameliorates insulin sensitivity and secretion without affecting obesity
Thioredoxin binding protein-2 (TBP-2) mutant mice have abnormal insulin sensitivity and secretion. In this study, TBP-2-null obese mice are shown to have improved insulin sensitivity and glucose intolerance, suggesting a potential role for TBP-2 inhibition in diabetes treatment.
- Eiji Yoshihara
- , Shimpei Fujimoto
- & Hiroshi Masutani
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Article
| Open AccessGlobal distribution of the sickle cell gene and geographical confirmation of the malaria hypothesis
Sixty years ago it was suggested that the sickle cell disease mutation survives because the heterozygous genotype confers resistance to malaria, resulting in correlation of the two geographical distributions. The authors use a new global assembly of sickle allele frequencies to support this hypothesis at the global scale.
- Frédéric B. Piel
- , Anand P. Patil
- & Simon I. Hay
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G-protein β2 subunit interacts with mitofusin 1 to regulate mitochondrial fusion
Little is known about the regulation of mitofusin proteins that are involved in the fusion of mitochondrial membranes. In this study, the authors report that a heterotrimeric G protein, Gβ-subunit 2, can interact with mitofusin 1, and is involved in the regulation of mitochondrial fusion.
- Juan Zhang
- , Weihua Liu
- & Quan Chen
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A role for TREX components in the release of spliced mRNA from nuclear speckle domains
The pre-mRNA splicing and TREX mRNA export machineries are found in nuclear speckle domains. Diaset al. microinject CMV-DNA constructs into cells and find that transcripts containing functional splice sites accumulate in nuclear speckles and that the TREX complex is required to release the mRNA once processed.
- Anusha P. Dias
- , Kobina Dufu
- & Robin Reed
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Calmodulin methyltransferase is an evolutionarily conserved enzyme that trimethylates Lys-115 in calmodulin
Calmodulin is a key mediator of calcium-dependent signalling and is subject to post-translational modifications. Here, evolutionarily conserved methyltransferases are identified which trimethylate Lys-115 of calmodulin, implying a broad role in calcium-dependent signalling.
- Roberta Magnani
- , Lynnette M.A. Dirk
- & Robert L. Houtz
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Article
| Open AccessDivergent transcriptional activities determine limb identity
The embryonic development of forelimbs and hindlimbs is regulated by transcription factors, including Pitx1, Tbx4 and Tbx5. In this study, the contributions of Tbx4 and Tbx5 to limb identity are further delineated, resulting in the demonstration of a role for Tbx4 in hindlimb skeletal and muscle patterning.
- Jean-François Ouimette
- , Marisol Lavertu Jolin
- & Jacques Drouin
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TERRA transcripts are bound by a complex array of RNA-binding proteins
Recent work has revealed that the TTAGGG DNA repeats of telomeres are transcribed to form 'TERRA'. In this study, a set of RNA-binding proteins are shown to bind TERRA transcripts, altering the location of these transcripts at telomeres and regulating telomere abundance and length.
- Isabel López de Silanes
- , Martina Stagno d'Alcontres
- & Maria A Blasco
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Article
| Open AccessOrganogenesis relies on SoxC transcription factors for the survival of neural and mesenchymal progenitors
During development Sox transcription factors play important roles in the determination of cell fate. In this study Bhattaram and colleagues show that Sox4, Sox11 and Sox12 act redundantly in mouse development and are important for the maintenance of neural and mesenchymal progenitor cells.
- Pallavi Bhattaram
- , Alfredo Penzo-Méndez
- & Véronique Lefebvre
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Article
| Open AccessA doublecortin containing microtubule-associated protein is implicated in mechanotransduction in Drosophila sensory cilia
Mechanoreceptors are important for detecting external stimuli. In this study a putative receptor identified inDrosophilais shown to be potentially important for hearing and the amplification of mechanotransduction.
- S. Bechstedt
- , J.T. Albert
- & J. Howard
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