Signal Transduction
- Differential roles of ERRFI1 in EGFR and AKT pathway regulation affect cancer proliferation
- Junmei Cairns1,
- Brooke L Fridley2,3,
- Gregory D Jenkins2,
- Yongxian Zhuang1,
- Jia Yu1 and
- Liewei Wang (wang.liewei{at}mayo.edu)*,1
- 1Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA
- 2Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
- 3Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, FL, USA
- ↵*Corresponding author. Tel: +1 507 284 5264; E‐mail: wang.liewei{at}mayo.edu
The ERBB receptor inhibitor ERRFI1 regulates AKT/EGFR signaling in an EGFR‐dependent manner. In EGFR‐low cells, ERRFI1 activates AKT by blocking the PHLPP‐AKT interaction. In EGFR‐high cells, ERRFI1 functions as a negative regulator of the EGFR pathway.
Synopsis
The ERBB receptor inhibitor ERRFI1 regulates AKT/EGFR signaling in an EGFR‐dependent manner. In EGFR‐low cells, ERRFI1 activates AKT by blocking the PHLPP‐AKT interaction. In EGFR‐high cells, ERRFI1 functions as a negative regulator of the EGFR pathway.
In EGFR‐low cells, ERRFI1 activates AKT and promotes proliferation and chemotherapy resistance.
In EGFR‐low cells, AKT inhibition is beneficial and increases chemosensitivity.
In EGFR‐high cells, reduced ERRFI1 leads to active EGFR and increased cell proliferation.
In EGFR‐high cells, EGFR inhibition is beneficial and sensitizes for chemotherapy.
EMBO Reports (2018) 19: e44767
- Received July 5, 2017.
- Revision received December 12, 2017.
- Accepted December 18, 2017.
- © 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.
- Metabolic stress regulates ERK activity by controlling KSR‐RAF heterodimerization
- Amandine Verlande1,2,
- Michaela Krafčíková3,
- David Potěšil3,
- Lukáš Trantírek3,
- Zbyněk Zdráhal3,
- Moustafa Elkalaf4,
- Jan Trnka4,
- Karel Souček1,5,6,
- Nora Rauch7,8,9,
- Jens Rauch7,8,9,
- Walter Kolch7,8,9 and
- Stjepan Uldrijan (uldrijan{at}med.muni.cz)*,1,2
- 1International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic
- 2Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
- 3Central European Institute of Technology, Masaryk University, Brno, Czech Republic
- 4Laboratory for Metabolism and Bioenergetics, Third Faculty of Medicine, Charles University, Prague, Czech Republic
- 5Laboratory of Cytokinetics, Institute of Biophysics, Academy of Sciences, Brno, Czech Republic
- 6Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic
- 7Systems Biology Ireland, University College Dublin, Dublin, Ireland
- 8Conway Institute, University College Dublin, Dublin, Ireland
- 9School of Medicine, University College Dublin, Dublin, Ireland
- ↵*Corresponding author. Tel: +420 549494040; E‐mail: uldrijan{at}med.muni.cz
Somatic RAF/RAS mutations result in deregulated ERK signaling in melanomas. Metabolic stress impacts differently on ERK activation in BRAF‐ and NRAS‐mutant cells, indicating that targeting of energy metabolism is not a general therapeutic strategy for melanoma.
Synopsis
Somatic RAF/RAS mutations result in deregulated ERK signaling in melanomas. Metabolic stress impacts differently on ERK activation in BRAF‐ and NRAS‐mutant cells, indicating that targeting of energy metabolism is not a general therapeutic strategy for melanoma.
Metabolic stress induces CRAF/KSR dimerization in NRAS‐mutant cells, increasing ERK activity.
Metabolically stressed BRAFV600E‐mutant cells show an interaction of KSR with oncogenic BRAF.
High metabolic stress leads to the dissociation of mutant BRAF from KSR, reducing ERK activity.
Successful metabolic targeting strategies depend on the RAS/RAF mutational status.
EMBO Reports (2018) 19: 320–336
- Received May 23, 2017.
- Revision received November 15, 2017.
- Accepted November 24, 2017.
- © 2017 The Authors
- WDR11‐mediated Hedgehog signalling defects underlie a new ciliopathy related to Kallmann syndrome
- Yeon‐Joo Kim1,
- Daniel PS Osborn1,
- Ji‐Young Lee1,
- Masatake Araki2,
- Kimi Araki2,
- Timothy Mohun3,
- Johanna Känsäkoski4,
- Nina Brandstack4,
- Hyun‐Taek Kim5,8,
- Francesc Miralles1,
- Cheol‐Hee Kim5,
- Nigel A Brown1,
- Hyung‐Goo Kim6,
- Juan Pedro Martinez‐Barbera7,
- Paris Ataliotis1,
- Taneli Raivio4,
- Lawrence C Layman6 and
- Soo‐Hyun Kim (skim{at}sgul.ac.uk)*,1
- 1Molecular and Clinical Sciences Research Institute, St. George's, University of London, London, UK
- 2Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Japan
- 3Francis Crick Institute, London, UK
- 4Helsinki University Central Hospital, Helsinki, Finland
- 5Department of Biology, Chungnam National University, Daejeon, Korea
- 6Medical College of Georgia, Augusta University, Augusta, GA, USA
- 7Developmental Biology and Cancer Programme, Birth Defects Research Centre, UCL Great Ormond Street Institute of Child Health, London, UK
- 8Present Address: Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
- ↵*Corresponding author. Tel: +44 2082666198; E‐mail: skim{at}sgul.ac.uk
WDR11, the causative gene for congenital hypogonadotrophic hypogonadism and Kallmann syndrome, promotes Hedgehog singaling and ciliogenesis, linking these diseases to the human ciliopathy spectrum.
Synopsis
WDR11, the causative gene for congenital hypogonadotrophic hypogonadism and Kallmann syndrome, promotes Hedgehog singaling and ciliogenesis, linking these diseases to the human ciliopathy spectrum.
WDR11 functions as a novel element of the Hedgehog (Hh) signal pathway, which regulates fundamental aspects of mammalian development.
WDR11 shuttles between the nucleus and cytoplasm in response to Hh‐signaling.
WDR11 is required for the processing of GLI3 protein, forms a tertiary complex with EMX1 and GLI3 and regulates the expression of novel target genes EMX1/2 and GNRH1.
WDR11 is a cilia‐associated protein suggesting that CHH/KS with WDR11 mutations are ciliopathy disorders.
EMBO Reports (2018) 19: 269–289
- Received June 13, 2017.
- Revision received November 14, 2017.
- Accepted November 17, 2017.
- © 2017 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- TRIP6 inhibits Hippo signaling in response to tension at adherens junctions
- Shubham Dutta1,
- Sebastian Mana‐Capelli1,
- Murugan Paramasivam1,
- Ishani Dasgupta1,
- Heather Cirka2,
- Kris Billiar2 and
- Dannel McCollum (dannel.mccollum{at}umassmed.edu)*,1
- 1Department of Biochemistry & Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA
- 2Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, USA
- ↵*Corresponding author. Tel: +1 508 856 8767; E‐mail: dannel.mccollum{at}umassmed.edu
Mechanical tension regulates Hippo signaling via the mechanosensor vinculin at adherens junctions. Tension‐activated vinculin stimulates binding of LATS1/2 to TRIP6, which blocks the association of LATS1/2 with its activator MOB1, thereby increasing YAP activity.
Synopsis
Mechanical tension regulates Hippo signaling via the mechanosensor vinculin at adherens junctions. Tension‐activated vinculin stimulates binding of LATS1/2 to TRIP6, which blocks the association of LATS1/2 with its activator MOB1, thereby increasing YAP activity.
TRIP6 and LATS1/2 interact at adherens junctions in a tension‐dependent manner.
TRIP6 inhibits LATS1/2 by competing for its interaction with the activator protein MOB1.
Vinculin recruits TRIP6 to adherens junctions to activate YAP in response to mechanical tension.
EMBO Reports (2018) 19: 337–350
- Received July 6, 2017.
- Revision received November 13, 2017.
- Accepted November 15, 2017.
- © 2017 The Authors
- A kinase‐dependent role for Haspin in antagonizing Wapl and protecting mitotic centromere cohesion
- Cai Liang1,†,
- Qinfu Chen1,†,
- Qi Yi1,
- Miao Zhang1,
- Haiyan Yan1,
- Bo Zhang1,
- Linli Zhou1,
- Zhenlei Zhang1,
- Feifei Qi1,
- Sheng Ye1 and
- Fangwei Wang (fwwang{at}zju.edu.cn)*,1
- 1Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, China
- ↵*Corresponding author. Tel: +86 571 88206127; E‐mail: fwwang{at}zju.edu.cn
↵† These authors contributed equally to this work
Wapl releases the bulk of cohesin from chromosome arms in prophase, whereas centromeric cohesin is protected until anaphase onset. The kinase Haspin phosphorylates Wapl, thereby inhibiting the interaction with Pds5B, and protecting centromeric cohesion.
Synopsis
Wapl releases the bulk of cohesin from chromosome arms in prophase, whereas centromeric cohesin is protected until anaphase onset. The kinase Haspin phosphorylates Wapl, thereby inhibiting the interaction with Pds5B, and protecting centromeric cohesion.
The mitotic histone kinase Haspin binds and phosphorylates the cohesin‐releasing factor Wapl at its YSR motif.
Phosphorylated Wapl does not interact with the cohesin subunit Pds5B.
Haspin has a kinase‐dependent role in protecting centromeric cohesion during mitosis.
EMBO Reports (2018) 19: 43–56
- Received July 2, 2017.
- Revision received October 17, 2017.
- Accepted October 19, 2017.
- © 2017 The Authors
- NLRP11 disrupts MAVS signalosome to inhibit type I interferon signaling and virus‐induced apoptosis
- Yunfei Qin1,2,†,
- Zexiong Su1,†,
- Yaoxing Wu1,†,
- Chenglei Wu1,
- Shouheng Jin1,
- Weihong Xie1,
- Wei Jiang3,
- Rongbin Zhou3 and
- Jun Cui (cuij5{at}mail.sysu.edu.cn)*,1
- 1Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat‐sen University, Guangzhou, China
- 2School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China
- 3Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, CAS Center for Excellence in Molecular Cell Sciences, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, China
- ↵*Corresponding author. Tel: +86 20 39943429; E‐mail: cuij5{at}mail.sysu.edu.cn
↵† These authors contributed equally to this work
The MAVS signalosome mediates RIG‐I‐like receptor‐induced anti‐viral innate immune responses. NLRP11 inhibits MAVS‐dependent type I interferon signaling and virus‐induced apoptosis by disrupting the signalosome and promoting proteasomal degradation of TRAF6.
Synopsis
The MAVS signalosome mediates RIG‐I‐like receptor‐induced anti‐viral innate immune responses. NLRP11 inhibits MAVS‐dependent type I interferon signaling and virus‐induced apoptosis by disrupting the signalosome and promoting proteasomal degradation of TRAF6.
The Nod‐like receptor NLRP11 disrupts MAVS signalosomes by promoting TRAF6 degradation.
NLRP11 is induced by type I IFN upon viral infection and interacts with MAVS at mitochondria.
NLRP11 suppresses virus‐induced apoptosis in a MAVS‐dependent manner.
EMBO Reports (2017) 18: 2160–2171
- Received May 15, 2017.
- Revision received September 25, 2017.
- Accepted October 4, 2017.
- © 2017 The Authors
- TORC1 and TORC2 converge to regulate the SAGA co‐activator in response to nutrient availability
- Thomas Laboucarié1,
- Dylane Detilleux1,
- Ricard A Rodriguez‐Mias2,
- Céline Faux1,
- Yves Romeo1,5,
- Mirita Franz‐Wachtel3,
- Karsten Krug3,
- Boris Maček3,
- Judit Villén2,
- Janni Petersen4 and
- Dominique Helmlinger (dhelmlinger{at}crbm.cnrs.fr)*,1
- 1CRBM, CNRS, University of Montpellier, Montpellier, France
- 2Department of Genome Sciences, University of Washington, Seattle, WA, USA
- 3Proteome Center Tübingen, Tuebingen, Germany
- 4Flinders Centre for Innovation in Cancer, School of Medicine, Faculty of Health Science, Flinders University, Adelaide, SA, Australia
- 5Present Address: Laboratoire de Biologie Moléculaire Eucaryote, Université de Toulouse‐Paul Sabatier CNRS, UMR 5099, Toulouse, France
- ↵*Corresponding author. Tel: +33 434 35 95 48; Fax: +33 434 35 94 10; E‐mail: dhelmlinger{at}crbm.cnrs.fr
The Schizosaccharomyces pombe SAGA co‐activator regulates gene expression and cell fate decisions in response to nutrient availability. This study shows that TORC1 and TORC2 modulate the phosphorylation of the SAGA subunit Taf12, to control commitment to sexual differentiation upon starvation.
Synopsis
The Schizosaccharomyces pombe SAGA co‐activator regulates gene expression and cell fate decisions in response to nutrient availability. This study shows that TORC1 and TORC2 modulate the phosphorylation of the SAGA subunit Taf12, to control commitment to sexual differentiation upon starvation.
SAGA regulates nutrient‐responsive genes downstream of TORC1 and TORC2.
Starvation induces phosphorylation of a core SAGA component, Taf12, to control the timing and the amplitude of the differentiation response.
Taf12 phosphorylation is tuned by the opposing activities of the TORC1‐PP2A and TORC2‐AKT signaling pathways.
EMBO Reports (2017) 18: 2197–2218
- Received July 31, 2017.
- Revision received August 31, 2017.
- Accepted September 7, 2017.
- © 2017 The Authors
- Intersectin‐s interaction with DENND2B facilitates recycling of epidermal growth factor receptor
- Maria S Ioannou (maria.ioannou{at}mail.mcgill.ca)*,1,
- Gopinath Kulasekaran1,
- Maryam Fotouhi1,
- Justin J Morein1,
- Chanshuai Han1,
- Sarah Tse1,
- Nadya Nossova1,
- Tony Han1,
- Erin Mannard1 and
- Peter S McPherson (peter.mcpherson{at}mcgill.ca)*,1
- 1Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC, Canada
- ↵*
Corresponding author. Tel: +514 398 7355; E‐mail: maria.ioannou{at}mail.mcgill.ca
Corresponding author. Tel: +514 398 7355; E‐mail: peter.mcpherson{at}mcgill.ca
Whether EGFR is recycled or degraded is critical for growth signalling in cancer. The endocytic adaptor intersectin binds the Rab13 exchange factor DENND2B and drives unliganded EGFR into a recycling pathway, while EGF disrupts this interaction and targets EGFR for degradation.
Synopsis
Whether EGFR is recycled or degraded is critical for growth signalling in cancer. The endocytic adaptor intersectin binds the Rab13 exchange factor DENND2B and drives unliganded EGFR into a recycling pathway, while EGF disrupts this interaction and targets EGFR for degradation.
In the absence of EGF, DENND2B binds ITSN‐s driving internalized EGFR into a recycling pathway.
EGF promotes DENND2B phosphorylation by protein kinase D, disrupting the interaction with ITSN‐s.
In the absence of ITSN‐s interaction with DENND2B, EGFR is targeted for degradation.
EMBO Reports (2017) 18: 2119–2130
- Received February 4, 2017.
- Revision received September 19, 2017.
- Accepted September 20, 2017.
- © 2017 The Authors
- Lipids at membrane contact sites: cell signaling and ion transport
- 1Epithelial Signaling and Transport Section, National Institute of Dental and Craniofacial Research, Bethesda, MD, USA
- ↵*Corresponding author. Tel: +1 301 402 0262; E‐mail: shmuel.muallem{at}nih.gov
Communication between organelles occurs at membrane contact sites (MCSs) and allows the coordination of cellular functions and responses to various stimuli. This review discusses MCSs in the context of lipid transfer, the formation of lipid domains and Ca2+ signaling.
EMBO Reports (2017) 18: 1893–1904
- Received April 5, 2017.
- Revision received June 10, 2017.
- Accepted September 21, 2017.
- Published 2017. This article is a U.S. Government work and is in the public domain in the USA
- Antisense transcription represses Arabidopsis seed dormancy QTL DOG1 to regulate drought tolerance
- Ruslan Yatusevich1,
- Halina Fedak1,
- Arkadiusz Ciesielski2,
- Katarzyna Krzyczmonik1,
- Anna Kulik3,
- Grazyna Dobrowolska3 and
- Szymon Swiezewski (sswiez{at}ibb.waw.pl)*,1
- 1Department of Protein Biosynthesis, Institute of Biochemistry and Biophysics, Warsaw, Poland
- 2Department of Chemistry, Warsaw University, Warsaw, Poland
- 3Department of Plant Biochemistry, Institute of Biochemistry and Biophysics, Warsaw, Poland
- ↵*Corresponding author. Tel: +48 225925725; E‐mail: sswiez{at}ibb.waw.pl
Antisense transcription from the same locus is required for DOG1 silencing in mature Arabidopsis plants under non‐stress conditions. Drought and ABA signalling alleviate asDOG1 expression, promoting DOG1 sense transcription and drought tolerance.
Synopsis
Antisense transcription from the same locus is required for DOG1 silencing in mature Arabidopsis plants under non‐stress conditions. Drought and ABA signalling alleviate asDOG1 expression, promoting DOG1 sense transcription and drought tolerance.
Antisense DOG1 transcript (asDOG1) is negatively regulated by drought and ABA.
asDOG1 silencing results in DOG1 sense expression in mature Arabidopsis plants.
Antisense transcription is crucial for the perception of drought/ABA signals.
DOG1 confers drought tolerance.
EMBO Reports (2017) 18: 2186–2196
- Received July 19, 2017.
- Revision received September 8, 2017.
- Accepted September 15, 2017.
- © 2017 Institute of Biochemistry and Biophysics, Polish Academy of Sciences
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