Latest Online
- ArticleRNA sensor LGP2 inhibits TRAF ubiquitin ligase to negatively regulate innate immune signaling
- Jean‐Patrick Parisien1,†,
- Jessica J Lenoir1,†,
- Roli Mandhana1,
- Kenny R Rodriguez1,
- Kenin Qian1,
- Annie M Bruns2 and
- Curt M Horvath (horvath{at}northwestern.edu)*,1
- 1Department of Molecular Biosciences, Northwestern University, Evanston, IL, USA
- 2ATLAS Institute, University of Colorado, Boulder, CO, USA
- ↵*Corresponding author. Tel: +1 847 491 5530; Fax: +1 847 491 0848; E‐mail: horvath{at}northwestern.edu
↵† These authors contributed equally to this work
The innate immune RNA sensor LGP2 is a negative regulator of antiviral signal transduction. LGP2 interferes with TRAF ubiquitin ligase activity, thereby suppressing TRAF‐dependent signaling to prevent activation of IRF3 and NFκB.
Synopsis
The innate immune RNA sensor LGP2 is a negative regulator of antiviral signal transduction. LGP2 interferes with TRAF ubiquitin ligase activity, thereby suppressing TRAF‐dependent signaling to prevent activation of IRF3 and NFκB.
LGP2 interferes with IRF3 and NFκB antiviral signaling downstream of MAVS.
LGP2 co‐precipitates with and disrupts TRAF protein signaling and ubiquitin ligase activity.
LGP2 can act in trans to negatively regulate diverse TRAF signaling systems.
This regulatory activity does not depend on RNA binding, ATP hydrolysis, or its C‐terminal domain.
EMBO Reports (2018) e45176
- Received September 14, 2017.
- Revision received March 14, 2018.
- Accepted March 21, 2018.
- © 2018 The Authors
- OpinionPut science first and formatting later
- Aziz Khan (aziz.khan{at}ncmm.uio.no)1,
- Alejandro Montenegro‐Montero2,3 and
- Anthony Mathelier (anthony.mathelier{at}ncmm.uio.no)1,4
- 1Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo, Oslo, Norway
- 2Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Millennium Institute for Integrative Systems and Synthetic Biology (MIISSB), Pontificia Universidad Católica de Chile, Santiago, Chile
- 3John Wiley & Sons, Hoboken, NJ, USA
- 4Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway
Scientists spend considerable efforts with reformatting their research articles before each new submission. A widely adopted format‐free submission process would save them valuable time to do research instead.
- © 2018 The Authors
- Science & SocietySynthetic gene drive: between continuity and noveltyCrucial differences between gene drive and genetically modified organisms require an adapted risk assessment for their use
Crucial differences between gene drive and genetically modified organisms require an adapted risk assessment for their use
Gene drive organisms differ from “classical” genetically modified organisms in several crucial aspects. It would require new approaches for risk assessment to gauge their potential impact on the environment.
- © 2018 The Authors
- ArticleEphrinB2/EphB4 signaling regulates non‐sprouting angiogenesis by VEGF
- Elena Groppa1,2,5,†,
- Sime Brkic1,2,†,
- Andrea Uccelli1,2,
- Galina Wirth3,
- Petra Korpisalo‐Pirinen3,
- Maria Filippova1,2,
- Boris Dasen1,2,
- Veronica Sacchi1,2,6,
- Manuele Giuseppe Muraro1,2,
- Marianna Trani1,2,
- Silvia Reginato1,2,
- Roberto Gianni‐Barrera1,2,
- Seppo Ylä‐Herttuala3,4 and
- Andrea Banfi (andrea.banfi{at}usb.ch)*,1,2
- 1Department of Biomedicine, University Hospital, University of Basel, Basel, Switzerland
- 2Department of Surgery, University Hospital, Basel, Switzerland
- 3A. I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland
- 4Heart Center, Kuopio University Hospital, Kuopio, Finland
- 5Present Address: The Biomedical Research Centre, The University of British Columbia, Vancouver, BC, Canada
- 6Present Address: Genomics Institute of the Novartis Research Foundation, San Diego, CA, USA
- ↵*Corresponding author. Tel: +41 61 265 3507; Fax: +41 61 265 3990; E‐mail: andrea.banfi{at}usb.ch
↵† These authors contributed equally to this work
EphrinB2/EphB4 signalling between pericytes and endothelium regulates the switch from normal to aberrant angiogenesis caused by increasing VEGF doses. Pharmacologic stimulation of EphB4 ensures exclusively physiological vessel growth under therapeutically relevant conditions of VEGF gene delivery.
Synopsis
EphrinB2/EphB4 signalling between pericytes and endothelium regulates the switch from normal to aberrant angiogenesis caused by increasing Vascular endothelial growth factor (VEGF) doses. Pharmacologic stimulation of EphB4 ensures exclusively physiological vessel growth under therapeutically relevant conditions of VEGF gene delivery.
The endothelial tyrosine kinase receptor EphB4 finely tunes the degree of endothelial proliferation by specific VEGF doses in vivo.
EphB4 does not affect VEGF‐R2 activation or internalization, but regulates its downstream signaling through p‐ERK1/2.
EphB4 stimulation limits the size of circumferential vessel enlargement induced by VEGF, thereby enabling splitting into normal capillaries and preventing aberrant growth into angiomas.
EMBO Reports (2018) e45054
- Received August 23, 2017.
- Revision received March 3, 2018.
- Accepted March 8, 2018.
- © 2018 The Authors. Published under the terms of the CC BY NC ND 4.0 license
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs 4.0 License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
- ArticleCross‐talk between monocyte invasion and astrocyte proliferation regulates scarring in brain injury
- Jesica Frik1,2,3,
- Juliane Merl‐Pham4,
- Nikolaus Plesnila5,6,
- Nicola Mattugini1,2,7,
- Jacob Kjell1,2,
- Jonas Kraska1,
- Ricardo M Gómez3,
- Stefanie M Hauck4,
- Swetlana Sirko (swetlana.sirko{at}med.uni-muenchen.de)*,1,2 and
- Magdalena Götz (magdalena.goetz{at}helmholtz-muenchen.de)*,1,2,6
- 1Physiological Genomics, Biomedical Center, Ludwig‐Maximilians‐University Munich, Munich, Germany
- 2Institute for Stem Cell Research, Helmholtz Center Munich, Munich, Germany
- 3Instituto de Biotecnología y Biología Molecular, UNLP‐CONICET, La Plata, Argentina
- 4Research Unit for Protein Science, Helmholtz Center Munich, Munich, Germany
- 5Institute for Stroke and Dementia Research, Experimental Stroke Research, University of Munich Medical School, Munich, Germany
- 6SYNERGY, Excellence Cluster Systems Neurology, University of Munich, Munich, Germany
- 7Graduate School of Systemic Neurosciences, Biocenter, Ludwig‐Maximilians‐University of Munich, Munich, Germany
- ↵*
Corresponding author. Tel: +49 89 2180 75255; E‐mail: swetlana.sirko{at}med.uni-muenchen.de
Corresponding author. Tel: +49 89 2180 75255; E‐mail: magdalena.goetz{at}helmholtz-muenchen.de
Astrocytes resume proliferation specifically at the vascular wall after brain injury. Genetic increase of astrocyte proliferation reduces monocyte invasion at the injury site, while lack of monocyte invasion promotes astrocyte proliferation and reduces the GFAP+ scar.
Synopsis
Astrocytes resume proliferation specifically at the vascular wall after brain injury. Genetic increase of astrocyte proliferation reduces monocyte invasion at the injury site, while lack of monocyte invasion promotes astrocyte proliferation and reduces the GFAP+ scar.
Reactive astrocytes proliferate at blood vessels after brain injury and show nuclear localisation of the aryl hydrocarbon receptor.
Increased juxtavascular astrocyte proliferation decreases monocyte invasion at the injury site.
Block of monocyte invasion in CCR2−/− mice leads to increased juxtavascular astrocyte proliferation and reduced scar formation.
EMBO Reports (2018) e45294
- Received October 6, 2017.
- Revision received March 2, 2018.
- Accepted March 9, 2018.
- © 2018 The Authors. Published under the terms of the CC BY NC ND 4.0 license
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs 4.0 License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
- Scientific ReportDisentangling the molecular determinants for Cenp‐F localization to nuclear pores and kinetochores
- Alessandro Berto1,2,
- Jinchao Yu3,
- Stéphanie Morchoisne‐Bolhy1,
- Chiara Bertipaglia4,
- Richard Vallee4,
- Julien Dumont1,
- Francoise Ochsenbein3,
- Raphael Guerois3 and
- Valérie Doye (valerie.doye{at}ijm.fr)*,1
- 1Institut Jacques Monod, UMR7592, CNRS, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
- 2Ecole Doctorale Structure et Dynamique des Systèmes Vivants (#577), Univ Paris Sud, Université Paris‐Saclay, Orsay, France
- 3Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ Paris Sud, Université Paris‐Saclay, Gif sur Yvette, France
- 4Department of Pathology and Cell Biology, Columbia University, New York, NY, USA
- ↵*Corresponding author. Tel: +33 1 57 27 80 62; E‐mail: valerie.doye{at}ijm.fr
Cenp‐F contributes to multiple processes throughout the cell cycle. Here, key residues required for Cenp‐F recruitment to nuclear pores or kinetochores are identified using in silico structural modelling, yeast two‐hybrid assays and localization studies.
Synopsis
Cenp‐F contributes to multiple processes throughout the cell cycle. Here, key residues required for Cenp‐F recruitment to nuclear pores or kinetochores are identified using in silico structural modelling, yeast two‐hybrid assays and localization studies.
A conserved helix within the Nup133 β‐propeller interacts with a leucine zipper‐containing dimeric segment of Cenp‐F.
The direct interaction with Bub1 is important for Cenp‐F recruitment to kinetochores.
Mutations within the Cenp‐F C‐terminus discriminate NPC/nuclear bodies from kinetochore targeting.
EMBO Reports (2018) e44742
- Received July 5, 2017.
- Revision received March 2, 2018.
- Accepted March 8, 2018.
- © 2018 The Authors
- ArticleRNase H eliminates R‐loops that disrupt DNA replication but is nonessential for efficient DSB repair
- ↵*Corresponding author. Tel: +1 858 784 8273; E‐mail: prussell{at}scripps.edu
↵† These authors contributed equally to this work
Yeast cells lacking RNases H1 and H2 accumulate RNA–DNA hybrids that trigger replication fork collapse, but RNases H1/H2 are not generally required for efficient double‐strand break repair.
Synopsis
Yeast cells lacking RNases H1 and H2 accumulate RNA–DNA hybrids that trigger replication fork collapse, but RNases H1/H2 are not generally required for efficient double‐strand break repair.
RNase H1/H2‐deficient cells are fully able to repair double‐strand breaks formed by ionizing radiation.
RNase H1/H2 mutants accumulate RNA–DNA hybrids at tRNA and rDNA genes but not at an efficiently repaired double‐strand break.
Recombinational repair proteins, Mus81 resolvase and Rad3/ATR‐Chk1 checkpoint proteins are crucial for cellular survival in the absence of RNases H1/H2.
EMBO Reports (2018) e45335
- Received October 16, 2017.
- Revision received March 2, 2018.
- Accepted March 9, 2018.
- © 2018 The Authors
