Signal Transduction
- miR‐10b expression in breast cancer stem cells supports self‐renewal through negative PTEN regulation and sustained AKT activation
- Ivan Bahena‐Ocampo1,
- Magali Espinosa1,
- Gisela Ceballos‐Cancino1,
- Floria Lizarraga1,
- Denise Campos‐Arroyo1,
- Angela Schwarz1,
- Vilma Maldonado1 and
- Jorge Melendez‐Zajgla*,1
- 1Basic Research Subdivision, National Institute of Genomic Medicine, Functional Genomics Laboratory, Mexico City, Mexico
- ↵*Corresponding author. Tel: +52 5553 501920; E‐mail: jmelendez{at}inmegen.gob.mx
The oncogenic microRNA miR‐10b regulates the stem phenotype of breast cancer cells. This is accomplished by targeting the PTEN tumor suppressor gene, which in turns increases the activation of Akt.
Synopsis
The oncogenic microRNA miR‐10b regulates the stem phenotype of breast cancer cells. This is accomplished by targeting the PTEN tumor suppressor gene, which in turns increases the activation of Akt.
miR‐10b is overexpressed in breast cancer stem cells.
It regulates the number of stem cells and stem cell markers in breast cancer cell lines.
miR‐10b targets PTEN, which in turn activates Akt. PTEN is needed for the effects of miR‐10b on the stem phenotype.
EMBO Reports (2016) 17: 648–658
- Received May 20, 2015.
- Revision received February 20, 2016.
- Accepted March 4, 2016.
- © 2016 The Authors
- Sonic hedgehog is a regulator of extracellular glutamate levels and epilepsy
- Shengjie Feng1,2,†,
- Shaorong Ma1,2,†,
- Caixia Jia1,†,
- Yujuan Su1,2,
- Shenglian Yang1,
- Kechun Zhou1,
- Yani Liu3,
- Ju Cheng1,2,
- Dunguo Lu1,
- Liu Fan1 and
- Yizheng Wang*,1
- 1Laboratory of Neural Signal Transduction, Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
- 2University of Chinese Academy of Sciences, Shanghai, China
- 3Center of Cognition and Brain Science, AMMS, Beijing, China
- ↵*Corresponding author. Tel: +86 21 5492 1793; Fax: +86 21 5492 1735; E‐mail: yzwang{at}ion.ac.cn
↵† These authors contributed equally to this work
This study shows that sonic hedgehog (Shh) can regulate extracellular glutamate levels, which has implications for neuronal activity and epilepsy.
Synopsis
This study shows that sonic hedgehog (Shh) can regulate extracellular glutamate levels, which has implications for neuronal activity and epilepsy.
Shh is specifically released in response to epileptic stimulations, but not upon physiological stimulations.
Shh enhances extracellular glutamate levels by inhibiting glutamate transporter activities in a manner that is dependent on Gαi3.
Inhibition of Shh pathways markedly suppressed the development of epilepsy.
EMBO Reports (2016) 17: 682–694
- Received October 14, 2015.
- Revision received March 1, 2016.
- Accepted March 7, 2016.
- © 2016 The Authors
- An essential role for Grk2 in Hedgehog signalling downstream of Smoothened
- Zhonghua Zhao1,2,†,
- Raymond Teck Ho Lee2,†,
- Ganesh V Pusapati3,
- Audrey Iyu2,
- Rajat Rohatgi3 and
- Philip W Ingham*,1,2
- 1Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
- 2Developmental and Biomedical Genetics Laboratory, Institute of Molecular and Cell Biology, Agency of Science, Technology and Research (A‐STAR), Singapore, Singapore
- 3Departments of Medicine and Biochemistry, School of Medicine, Stanford University, Stanford, CA, USA
- ↵*Corresponding author. Tel: +65 65869736; E‐mail: pingham{at}ntu.edu.sg
↵† These authors contributed equally to this work
Loss of zebrafish Grk2 eliminates all responses to Hh signalling during embryogenesis, but phospho‐null mutants of Smo retain significant activity, suggesting that Smo is not the principal target of Grk2.
Synopsis
Loss of zebrafish Grk2 eliminates all responses to Hh signalling during embryogenesis, but phospho‐null mutants of Smo retain significant activity, suggesting that Smo is not the principal target of Grk2.
Grk2 is essential for all responses to Hh signalling in the zebrafish embryo.
Phosphorylation of Grk2/CK1 sites in the Smo CTT is neither necessary nor sufficient for its activation.
Grk2 regulates Hh signalling downstream of Smo, possibly via an unidentified GPCR.
EMBO Reports (2016) 17: 739–752
- Received October 7, 2015.
- Revision received March 7, 2016.
- Accepted March 7, 2016.
- © 2016 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.
- Lrig1 is a cell‐intrinsic modulator of hippocampal dendrite complexity and BDNF signaling
- Fernando Cruz Alsina1,†,
- Francisco Javier Hita1,†,
- Paula Aldana Fontanet1,
- Dolores Irala1,
- Håkan Hedman2,
- Fernanda Ledda1 and
- Gustavo Paratcha*,1
- 1Division of Molecular and Cellular Neuroscience, Institute of Cell Biology and Neuroscience (IBCN)‐CONICET School of Medicine University of Buenos Aires (UBA), Buenos Aires, Argentina
- 2Oncology Research Laboratory, Department of Radiation Sciences, Umeå University, Umeå, Sweden
- ↵*Corresponding author. Tel: +54 11 5950‐9500; Fax: +54 11 5950‐9626; E‐mails: gparatcha{at}fmed.uba.ar or gustavo.paratcha{at}conicet.gov.ar
↵† These authors contributed equally to this study
Lrig1 regulates dendritogenesis and apical dendrite branching of CA1–CA3 pyramidal hippocampal neurons in vivo, acting as an endogenous inhibitor of neurotrophin‐induced proximal dendrite arborization of pyramidal hippocampal neurons.
Synopsis
Lrig1 is a novel regulator of dendritogenesis and apical dendrite branching of CA1–CA3 pyramidal hippocampal neurons in vivo, acting as an endogenous inhibitor of neurotrophin‐induced proximal dendrite arborization of pyramidal hippocampal neurons.
Lrig1 is a physiological regulator of hippocampal dendrite development.
Lrig1 is required for proper apical dendrite arborization of CA1–CA3 pyramidal neurons and social behavior.
Lrig1 controls TrkB signaling and dendrite development induced by BDNF.
EMBO Reports (2016) 17: 601–616
- Received August 19, 2015.
- Revision received January 26, 2016.
- Accepted January 28, 2016.
- © 2016 The Authors
- Yap1 is dispensable for self‐renewal but required for proper differentiation of mouse embryonic stem (ES) cells
- 1Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, TX, USA
- ↵*Corresponding author. Tel: +1 512 232 8046; E‐mail: jonghwankim{at}mail.utexas.edu
Until recently, the roles of Yap1 in mouse embryonic stem (ES) cells have been elusive. This study shows that Yap1 is a critical regulator for proper differentiation but that it is dispensable for self‐renewal of ES cells.
Synopsis
Until recently, the roles of Yap1 in mouse embryonic stem (ES) cells have been elusive. This study shows that Yap1 is a critical regulator for proper differentiation but that it is dispensable for self‐renewal of ES cells.
Yap1‐depleted ES cells maintain an undifferentiated state.
Yap1‐associated factors, Taz and Tead family proteins are not essential for the self‐renewal of ES cells.
Yap1 is induced and translocated into the nucleus upon differentiation of ES cells.
Yap1 is required for the proper differentiation of ES cells.
EMBO Reports (2016) 17: 519–529
- Received June 24, 2015.
- Revision received January 8, 2016.
- Accepted January 22, 2016.
- © 2016 The Authors
- NAT10 regulates p53 activation through acetylating p53 at K120 and ubiquitinating Mdm2
- Xiaofeng Liu1,2,
- Yuqin Tan1,2,
- Chunfeng Zhang1,3,
- Ying Zhang1,4,
- Liangliang Zhang1,2,
- Pengwei Ren1,2,
- Hongkui Deng1,2,
- Jianyuan Luo1,3,5,
- Yang Ke1,4 and
- Xiaojuan Du*,1,2
- 1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing, China
- 2Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
- 3Department of Medical Genetics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
- 4Laboratory of Genetics, Peking University School of Oncology, Peking University Cancer Hospital & Institute, Beijing, China
- 5Department of Medical & Research Technology, School of Medicine, University of Maryland, Baltimore, MD, USA
- ↵*Corresponding author. Tel: +86 10 82801547; Fax: +86 10 82801130; E‐mail: duxiaojuan100{at}bjmu.edu.cn
NAT10 acts as an E3 ligase for Mdm2 to promote Mdm2 degradation and stabilizes p53 under normal conditions. While under DNA damage conditions, NAT10 prevents Mdm2–p53 interaction by binding to p53 and acetylates p53, thus regulating p53‐mediated cell cycle arrest and apoptosis.
Synopsis
NAT10 acts as an E3 ligase for Mdm2 to promote Mdm2 degradation and stabilizes p53 under normal conditions. While under DNA damage conditions, NAT10 prevents Mdm2–p53 interaction by binding to p53 and acetylates p53, thus regulating p53‐mediated cell cycle arrest and apoptosis.
NAT10 promotes Mdm2 ubiquitination and degradation with its E3 ligase activity under normal conditions.
NAT10 acetylates p53 at K120.
NAT10 translocates to nucleoplasm to bind and acetylate p53 at K120 upon cellular stress, thus contributing to p53 activation.
EMBO Reports (2016) 17: 349–366
- Received April 7, 2015.
- Revision received November 14, 2015.
- Accepted January 11, 2016.
- © 2016 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.
- Role of Angiomotin‐like 2 mono‐ubiquitination on YAP inhibition
- 1National Creative Research Center for Cell Division and Differentiation, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea
- 2Center for Theragnosis, Biomedical Research Institute Korea Institute of Science and Technology (KIST), Seoul, Korea
- 3Department of Biological Chemistry, University of Science and Technology, Daejeon, Korea
- ↵*Corresponding author. Tel: +82 42 350 2635; E‐mail: daesiklim{at}kaist.ac.kr
↵† These authors contributed equally to this work
This study reports a new regulatory mechanism of the Hippo signaling governed by mono‐ubiquitination of AMOTL2. AMOTL2 mono‐ubiquitination is required to bind and activate LATS kinase and to inhibit YAP activity and is regulated by the USP9X deubiquitinase.
Synopsis
This study reports a new regulatory mechanism of the Hippo signaling governed by mono‐ubiquitination of AMOTL2. AMOTL2 mono‐ubiquitination is required to bind and activate LATS kinase and to inhibit YAP activity and is regulated by the USP9X deubiquitinase.
USP9X is a deubiquitinating enzyme activating YAP.
USP9X deubiquitinates AMOTL2 on its coiled‐coil domain.
Mono‐ubiquitination of AMOTL2 is required for its tumor suppressor function.
Mono‐ubiquitinated AMOTL2 activates LATS kinase through binding to the UBA domain of LATS.
EMBO Reports (2016) 17: 64–78
- Received June 6, 2015.
- Revision received October 16, 2015.
- Accepted October 20, 2015.
- © 2015 The Authors
- New frontiers: discovering cilia‐independent functions of cilia proteins
- 1Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA
- 2CRBM – CNRS Université de Montpellier, Montpellier, France
- 3Department of Cell and Developmental Biology, SUNY Upstate Medical University, Syracuse, NY, USA
- ↵*
Corresponding author. Tel: +1 315 464 8528; E‐mail: HehnlyH{at}upstate.edu
Corresponding author. Tel: +1 508 353 8904; E‐mail: Stephen.Doxsey{at}umassmed.edu
↵† These authors contributed equally to this work
Various cilia proteins are crucial for other cellular processes, such as regulation of the cell cycle, polarized membrane trafficking and the DNA damage response. Thus, so called “ciliopathies” may be caused not only—or not at all—by faulty cilia.
EMBO Reports (2015) 16: 1275–1287
- Received May 4, 2015.
- Revision received August 11, 2015.
- Accepted August 17, 2015.
- © 2015 The Authors
- EGFR kinase activity is required for TLR4 signaling and the septic shock response
- Saurabh Chattopadhyay1,†,
- Manoj Veleeparambil1,†,
- Darshana Poddar1,
- Samar Abdulkhalek1,
- Sudip K Bandyopadhyay1,
- Volker Fensterl1 and
- Ganes C Sen*,1
- ↵*Corresponding author. Tel: +1 216 444 0636; Fax: +1 216 444 0513; E‐mail: seng{at}ccf.org
↵† These authors contributed equally to this work
This study shows that EGFR kinase activity is necessary for the induction of interferon‐dependent, TLR4‐responsive genes. EGFR inhibition in vivo blocks septic shock and prevents death, suggesting a therapeutic avenue for this important pathology.
Synopsis
This study shows that EGFR kinase activity is necessary for the induction of interferon‐dependent, TLR4‐responsive genes. EGFR inhibition in vivo blocks septic shock and prevents death, suggesting a therapeutic avenue for this important pathology.
EGFR kinase activity differentially regulates TLR4‐induced gene expression.
EGFR activity is required for IRF activation.
EGFR activity is required for PI3K/AKT‐dependent phosphorylation of β‐catenin, a co‐activator of IRF3.
In vivo administration of an EGFR kinase inhibitor protects mice from LPS‐induced septic shock.
EMBO Reports (2015) 16: 1535–1547
- Received March 8, 2015.
- Revision received August 10, 2015.
- Accepted August 17, 2015.
- © 2015 The Authors
- Hypoxia and loss of PHD2 inactivate stromal fibroblasts to decrease tumour stiffness and metastasis
- Chris D Madsen*,1,2,
- Jesper T Pedersen2,
- Freja A Venning2,
- Lukram Babloo Singh2,
- Emad Moeendarbary3,
- Guillaume Charras4,5,
- Thomas R Cox2,
- Erik Sahai*,1 and
- Janine T Erler*,2
- 1Tumour Cell Biology Laboratory, The Francis Crick Institute (formerly Cancer Research UK London Research Institute), London, UK
- 2Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark
- 3Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
- 4Department of Cell and Developmental Biology, University College London, London, UK
- 5London Centre for Nanotechnology, University College London, London, UK
- ↵*
Corresponding author. Tel: +45 35 32 56 47; Fax: +45 35 32 56 69; E‐mail: chris.madsen{at}bric.ku.dk
Corresponding author. Tel: +44 20 7269 3165; E‐mail: erik.sahai{at}crick.ac.uk
Corresponding author. Tel: +45 35 32 56 66; Fax: +45 35 32 56 69; E‐mail: janine.erler{at}bric.ku.dk
Cancer‐associated fibroblasts induce cancer growth and spread. Here, chronic hypoxia and HIF‐1α stabilization are shown to deactivate CAFs, leading to impaired ECM remodelling and decreased metastasis in vivo.
Synopsis
Cancer‐associated fibroblasts—which are important mediators of cancer growth and spread—are shown to be deactivated by chronic hypoxia and HIF‐1α stabilization. Deactivated CAFs are impaired in ECM remodelling and lead to decreased metastasis in vivo.
Loss of PHD2 activity deactivates CAFs.
HIF‐1α suppresses αSMA expression.
Loss of PHD2 activity prevents CAF‐induced ECM remodelling.
Loss of PHD2 activity prevents CAF‐induced breast cancer metastasis.
EMBO Reports (2015) 16: 1394–1408
- Received January 16, 2015.
- Revision received August 4, 2015.
- Accepted August 4, 2015.
- © 2015 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.
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