Table of Contents
01 June 2018; volume 19, issue 6
Opinion
- Nobody at the top
Science bears some hallmarks of religion. But, unlike many organized religions, there is no central authority and no tenet remains unchallenged.
EMBO Reports (2018) 19: e46329
- © 2018 The Authors
- Transparency on scientific instruments
- 1Department of Management, School of Business and Social Sciences, Aarhus University, Aarhus, Denmark
- 2UTS Business School, University of Technology Sydney, Sydney, NSW, Australia
- 3School of Management, University of Bath, Bath, UK
- 4School of Biomedical Sciences, Queensland University of Technology, Brisbane, Qld, Australia
Scientists and commercial scientific instrument makers have a shared incentive against discloseing an instrument maker's contributions to research. Stricter rules to encourage reporting of such collaboration would help to improve transparency and reproducibility.
EMBO Reports (2018) 19: e45853
- © 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.
- Reproducibility crisis in science or unrealistic expectations?
The reproducibility crisis in biomedical research has spurred much debate about the causes of the failure to validate experimental results. But the discussion may be overlooking one crucial factor that is inherent to research with low sample sizes: random variation.
EMBO Reports (2018) 19: e46008
- © 2018 The Authors
News & Views
- Mitochondrial adaptation in obesity is a ClpPicated business
Quality control systems that maintain mitochondrial oxidative phosphorylation (OXPHOS) include rescue by mitochondrial fusion, elimination of dysfunctional mitochondria by mitophagy, and degradation of damaged proteins by proteases. ClpP is an ATP‐dependent protease located in the mitochondrial matrix and mutated in Perrault syndrome, causing gonadal atrophy and hearing loss. Given that hearing loss is common in mitochondrial diseases caused by mtDNA mutations, ClpP was proposed to be part of the quality control system to maintain proper mitochondrial OXPHOS function. Two recent studies independently report that deletion of ClpP in mice protects from insulin resistance and obesity by increasing mitochondrial OXPHOS capacity and browning in gonadal white adipose tissue and mitochondrial coupling in brown adipose tissue [1], [2]. Furthermore, liver‐ and muscle‐specific deletion of ClpP has no major effects on insulin resistance. These studies reveal that ClpP might be involved in tissue‐specific mitochondrial remodeling in response to metabolic demands, rather than exclusively removing damaged proteins to maintain OXPHOS capacity.
See also: Becker et al (May 2018) and Bhaskaran et al (March 2018)
Two recent studies independently show that loss of the mitochondrial protease ClpP protects mice from insulin resistance and diet‐induced obesity.
EMBO Reports (2018) 19: e46295
- © 2018 The Authors
Science & Society
- Bringing bioinformatics to the scientific massesAs the demand for high‐level bioinformatics is growing, training students in the field becomes ever more important
As the demand for high‐level bioinformatics is growing, training students in the field becomes ever more important
- David R Smith (dsmit242{at}uwo.ca)1
The deluge of sequencing and other data has spurred a growing demand for qualified bioinformaticians. Training the next generation of students to acquire the necessary skills is a major challenge for biology.
EMBO Reports (2018) 19: e46262
- © 2018 The Author
- The microbiome and its publicsA participatory approach for engaging publics with the microbiome and its implications for health and hygiene
A participatory approach for engaging publics with the microbiome and its implications for health and hygiene
Our project to engage members of the public with metagenomics of microbiota in their households yielded interesting results about their perception of health and hygiene. These findings could direct health‐oriented research and help scientists to navigate the social contexts or microbiome research.
EMBO Reports (2018) 19: e45786
- © 2018 The Authors
- A DEAL for open accessThe negotiations between the German DEAL project and publishers have global implications for academic publishing beyond just Germany
The negotiations between the German DEAL project and publishers have global implications for academic publishing beyond just Germany
- Philip Hunter, Freelance journalist (ph{at}philiphunter.com)1
The German DEAL project negotiates full open access publishing with the major publishers for many academic institutions in Germany. If successful, it could have a global impact on funders’ publishing policies.
- © 2018 The Author
Scientific Reports
- PRDM4 mediates YAP‐induced cell invasion by activating leukocyte‐specific integrin β2 expression
- Huan Liu1,†,
- Xiaoming Dai1,†,
- Xiaolei Cao1,†,
- Huan Yan1,
- Xinyan Ji1,
- Haitao Zhang1,
- Shuying Shen1,
- Yuan Si1,
- Hailong Zhang2,
- Jianfeng Chen2,
- Li Li3,
- Jonathan C Zhao4,
- Jindan Yu4,
- Xin‐Hua Feng1 and
- Bin Zhao (binzhao{at}zju.edu.cn)*,1
- 1Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang, China
- 2State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
- 3Institute of Aging Research, Hangzhou Normal University, Hangzhou, Zhejiang, China
- 4Department of Medicine‐Hematology/Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
- ↵*Corresponding author. Tel: +86 571 88208541; E‐mail: binzhao{at}zju.edu.cn
↵† These authors contributed equally to this work
Yes‐associated protein (YAP) is a transcriptional co‐activator and major effector of the Hippo pathway, promoting cell proliferation and stemness. YAP interacts with PRDM4, thereby promoting transendothelial invasion of cancer cells by inducing expression of the leukocyte‐specific integrin ITGB2.
Synopsis
Yes‐associated protein (YAP) is a transcriptional co‐activator and major effector of the Hippo pathway, promoting cell proliferation and stemness. YAP interacts with PRDM4, thereby promoting transendothelial invasion of cancer cells by inducing expression of the leukocyte‐specific integrin ITGB2.
PR/SET domain 4 (PRDM4) interacts with YAP to promote transcriptional activation of target genes.
PRDM4 and TEAD co‐ordinately mediate the activation of the YAP target gene ITGB2.
YAP‐induced ITGB2 expression promotes cancer cell invasion in a manner mimicking leukocytes.
EMBO Reports (2018) 19: e45180
- Received September 15, 2017.
- Revision received March 17, 2018.
- Accepted March 23, 2018.
- © 2018 The Authors
- Glutamine‐utilizing transaminases are a metabolic vulnerability of TAZ/YAP‐activated cancer cells
- Chih‐Sheng Yang1,†,
- Eleni Stampouloglou1,†,
- Nathan M Kingston1,†,
- Liye Zhang2,3,
- Stefano Monti2 and
- Xaralabos Varelas (xvarelas{at}bu.edu)*,1
- 1Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA
- 2Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA
- 3Present Address: School of Life Science and Technology, ShanghaiTech University, Shanghai, China
- ↵*Corresponding author. Tel: +1 617 358 4575; E‐mail: xvarelas{at}bu.edu
↵† These authors contributed equally to this work
Elevated levels of the transcriptional regulators TAZ/YAP, key effectors of Hippo pathway signalling, mediate breast cancer cell growth dependence on exogenous glutamine. Cancer cells with high TAZ/YAP activity are sensitive to transaminase inhibition.
Synopsis
Elevated levels of the transcriptional regulators TAZ/YAP, key effectors of Hippo pathway signalling, mediate breast cancer cell growth dependence on exogenous glutamine. Cancer cells with high TAZ/YAP activity are sensitive to transaminase inhibition.
High TAZ/YAP levels alter cellular energetics to promote breast cancer cell growth dependence on exogenous glutamine.
TAZ/YAP promote the expression of glutamic–oxaloacetic transaminase (GOT1) and phosphoserine aminotransferase (PSAT1).
Transaminase inhibition represses breast cancer cell growth in a TAZ/YAP dependent manner.
EMBO Reports (2018) 19: e43577
- Received October 26, 2016.
- Revision received March 19, 2018.
- Accepted March 23, 2018.
- © 2018 The Authors
- CD36 initiates the secretory phenotype during the establishment of cellular senescence
- Mengyang Chong1,†,
- Tao Yin1,†,
- Rui Chen1,
- Handan Xiang1,
- Lifeng Yuan1,
- Yi Ding1,
- Christopher C Pan1,
- Zhen Tang1,
- Peter B Alexander1,
- Qi‐Jing Li (qi-jing.li{at}duke.edu)*,2 and
- Xiao‐Fan Wang (xiao.fan.wang{at}duke.edu)*,1
- 1Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA
- 2Department of Immunology, Duke University, Durham, NC, USA
- ↵*
Corresponding author. Tel: +1 919 668 4070; E‐mail: qi-jing.li{at}duke.edu
Corresponding author. Tel: +1 919 681 4861; E‐mail: xiao.fan.wang{at}duke.edu
↵† These authors contributed equally to this work
The scavenger receptor CD36 and its ligand amyloid beta trigger NF‐κB pathway activation and the acquisition of a senescence‐associated secretory phenotype (SASP) in response to various senescence‐inducing stimuli.
Synopsis
In response to various senescence‐inducing stimuli, normal mammalian cells rapidly upregulate the scavenger receptor CD36. Amyloid beta‐dependent CD36 signaling then triggers NF‐κB pathway activation, resulting in the production and secretion of numerous inflammatory proteins known to comprise the senescence‐associated secretory phenotype.
The multi‐ligand receptor CD36 is induced in multiple senescence contexts.
Amyloid beta activates CD36 to stimulate NF‐κB‐dependent cytokine and chemokine production.
Sustained secretory molecule production leads to the onset of a comprehensive senescent cell fate.
EMBO Reports (2018) 19: e45274
- Received October 2, 2017.
- Revision received March 8, 2018.
- Accepted March 23, 2018.
- © 2018 The Authors
Articles
- The heptad repeat domain 1 of Mitofusin has membrane destabilization function in mitochondrial fusion
- Frédéric Daste1,2,†,
- Cécile Sauvanet3,5,†,
- Andrej Bavdek1,2,
- James Baye1,2,
- Fabienne Pierre1,2,4,
- Rémi Le Borgne2,
- Claudine David3,
- Manuel Rojo3,
- Patrick Fuchs2,6 and
- David Tareste (david.tareste{at}inserm.fr)*,1,2,4
- 1Membrane Traffic in Health & Disease, INSERM ERL U950, Sorbonne Paris Cité, Université Paris Descartes, Paris, France
- 2Institut Jacques Monod, CNRS UMR 7592, Sorbonne Paris Cité, Université Paris Diderot, Paris, France
- 3Institut de Biochimie et Génétique Cellulaires, CNRS UMR 5095, Université de Bordeaux, Bordeaux, France
- 4Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Sorbonne Paris Cité, Université Paris Descartes, Paris, France
- 5Present Address: Department of Molecular Biology and Genetics, Weill Institute for Molecular and Cell Biology, Cornell University, Ithaca, NY, USA
- 6Present Address: École Normale Supérieure, Laboratoire des Biomolécules, CNRS UMR 7203, Sorbonne Universités, Paris Sciences et Lettres Université, Université Pierre et Marie‐Curie, Paris, France
- ↵*Corresponding author. Tel: +33 1 40 78 92 49; E‐mail: david.tareste{at}inserm.fr
↵† These authors contributed equally to this work
The GTPase Mitofusin mediates mitochondrial fusion, but the underlying mechanism of membrane fusion remains unclear. This study shows that the amphipathic nature of the heptad repeat domain 1 (HR1) of Mitofusin perturbs the lipid bilayer structure to drive mitochondrial fusion.
Synopsis
The GTPase Mitofusin mediates mitochondrial fusion, but the underlying mechanism of membrane fusion remains unclear. This study shows that the amphipathic nature of the heptad repeat domain 1 (HR1) of Mitofusin perturbs the lipid bilayer structure to drive mitochondrial fusion.
HR1 is required for Mitofusin‐mediated mitochondrial fusion in cultured cells, and induces liposome fusion in vitro.
The membrane fusion activity of HR1 is associated with its capacity to insert into lipid bilayers, notably in regions presenting lipid packing defects.
This property is conferred by a conserved amphipathic helix located at the C‐terminus of the HR1 sequence.
EMBO Reports (2018) 19: e43637
- Received November 7, 2016.
- Revision received March 7, 2018.
- Accepted March 16, 2018.
- © 2018 The Authors
- RKIP mediates autoimmune inflammation by positively regulating IL‐17R signaling
- Wenlong Lin1,2,†,
- Ning Wang1,†,
- Kangxing Zhou3,†,
- Fasheng Su1,
- Yu Jiang4,
- Jianan Shou1,
- Huan Liu1,
- Chunmei Ma1,
- Youchun Qian5,
- Kai Wang2 and
- Xiaojian Wang (wangxiaojian{at}cad.zju.edu.cn)*,1
- 1Institute of Immunology, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
- 2Department of Respiratory Medicine, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
- 3Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
- 4Department of Clinical Laboratory Medicine, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
- 5The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai, China
- ↵*Corresponding author. Tel: +86 571 88206268; Fax: +86 571 88208285; E‐mail: wangxiaojian{at}cad.zju.edu.cn
↵† These authors contributed equally to this work
The Raf‐1 kinase inhibitor protein participates in the pathogenesis of IL‐17‐mediated autoimmune diseases and inflammation by promoting the formation of the IL‐17RA‐Act1 complex, required for downstream signaling and cytokine production.
Synopsis
The Raf‐1 kinase inhibitor protein participates in the pathogenesis of IL‐17‐mediated autoimmune diseases and inflammation by promoting the formation of the IL‐17RA‐Act1 complex, required for downstream signaling and cytokine production.
RIPK promotes EAE pathogenesis via enhanced IL‐17R‐mediated signaling and inflammation.
RKIP positively regulates IL‐17‐induced inflammation in vitro and in vivo.
RKIP interacts with IL‐17R and Act1, thereby stabilizing the IL‐17R‐Act1 complex.
EMBO Reports (2018) 19: e44951
- Received August 3, 2017.
- Revision received March 9, 2018.
- Accepted March 20, 2018.
- © 2018 The Authors
- RNA 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) 19: e45176
- Received September 14, 2017.
- Revision received March 14, 2018.
- Accepted March 21, 2018.
- © 2018 The Authors
- Opposing roles of miR‐294 and MBNL1/2 in shaping the gene regulatory network of embryonic stem cells
- Da‐Ren Wu1,†,
- Kai‐Li Gu1,†,
- Jian‐Cheng Yu2,
- Xing Fu3,
- Xi‐Wen Wang1,
- Wen‐Ting Guo1,
- Le‐Qi Liao1,
- Hong Zhu2,
- Xiao‐Shan Zhang1,
- Jingyi Hui (jyhui{at}sibcb.ac.cn)*,2 and
- Yangming Wang (yangming.wang{at}pku.edu.cn)*,1
- 1Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China
- 2State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China
- 3Shanghai Center for Plant Stress Biology, Chinese Academy of Sciences, Shanghai, China
- ↵*
Corresponding author. Tel: +86 21 5492 1354; E‐mail: jyhui{at}sibcb.ac.cn
Corresponding author. Tel: +86 10 6276 6945; E‐mail: yangming.wang{at}pku.edu.cn
↵† These authors contributed equally to this work
Extensive crosstalk between microRNAs and alternative splicing programs shapes the transcriptome of ESCs. The miR‐290/302 family and Mbnl1/2 proteins opposingly regulate alternative splicing and gene expression, thereby influencing cell fate determination.
Synopsis
Extensive crosstalk between microRNAs and alternative splicing programs shapes the transcriptome of ESCs. The miR‐290/302 family and Mbnl1/2 proteins opposingly regulate alternative splicing and gene expression, thereby influencing cell fate determination.
A subset of alternative splicing events in ESCs depends on the miR‐290/302 family.
miR‐294 regulates alternative splicing events by repressing the splicing regulators Mbnl1/2.
Mbnl1/2 counteracts miR‐294 by binding and promoting the expression of its key targets.
EMBO Reports (2018) 19: e45657
- Received December 16, 2017.
- Revision received April 3, 2018.
- Accepted April 11, 2018.
- © 2018 The Authors
- eIF5A is required for autophagy by mediating ATG3 translation
- Michal Lubas1,
- Lea M Harder2,
- Caroline Kumsta3,
- Imke Tiessen1,
- Malene Hansen3,
- Jens S Andersen2,
- Anders H Lund (anders.lund{at}bric.ku.dk)*,1 and
- Lisa B Frankel (lisa.frankel{at}bric.ku.dk)*,1
- 1Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark
- 2Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark
- 3Program of Development, Aging and Regeneration, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA
- ↵*
Corresponding author. Tel: +45 35325657; E‐mail: anders.lund{at}bric.ku.dk
Corresponding author. Tel: +45 35325813; E‐mail: lisa.frankel{at}bric.ku.dk
eIF5A is required for lipidation of ATG8 proteins and autophagosome formation. This results from eIF5A‐mediated translation of the E2‐like ATG3 protein, which contains an amino acid motif causing eIF5A dependency for its efficient translation.
Synopsis
Eukaryotic translation initiation factor 5A (eIF5A) is required for lipidation of ATG8 proteins and autophagosome formation. This results from eIF5A‐mediated translation of the E2‐like ATG3 protein, which contains an amino acid motif causing eIF5A dependency for its efficient translation.
A high‐throughput screen identifies eIF5A as a translational requirement of autophagy.
eIF5A facilitates autophagosome formation by facilitating translation of ATG3.
A tri‐peptide motif in ATG3 causes eIF5A dependency for its efficient translation.
Induction of autophagy causes enhanced association of eIF5A with the ribosome.
EMBO Reports (2018) 19: e46072
- Received March 7, 2018.
- Revision received March 26, 2018.
- Accepted April 6, 2018.
- © 2018 The Authors
