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  • Gcn5 and PCAF negatively regulate interferon‐β production through HAT‐independent inhibition of TBK1
    1. Qihuang Jin1,2,,
    2. Lenan Zhuang1,,
    3. Binbin Lai1,,
    4. Chaochen Wang1,,
    5. Wenqian Li2,
    6. Brian Dolan3,,
    7. Yue Lu2,
    8. Zhibin Wang4,,
    9. Keji Zhao4,,
    10. Weiqun Peng5,
    11. Sharon Y R Dent*,2 and
    12. Kai Ge*,1,
    1. 1Laboratory of Endocrinology and Receptor Biology, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD, USA
    2. 2Department of Molecular Carcinogenesis, Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Smithville, TX, USA
    3. 3Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA
    4. 4Systems Biology Center, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA
    5. 5Department of Physics, The George Washington University, Washington, DC, USA
    1. * Corresponding author. Tel: +1 512 237 2403; E‐mail: sroth{at}mdanderson.org

      Corresponding author. Tel: +1 301 451 1998; E‐mail: kaig{at}niddk.nih.gov

    1. Equal contribution

    2. This article has been contributed to by US Government employees and their work is in the public domain in the USA

    This study shows that, contrary to the current model and despite their recruitment to the IFNB promoter, Gcn5 and PCAF negatively regulate IFN‐β production. They do so in a histone acetyltransferase‐independent manner, through the inhibition of TBK1.

    Synopsis

    This study shows that, contrary to the current model and despite their recruitment to the IFNB promoter, Gcn5 and PCAF negatively regulate IFN‐β production. They do so in a histone acetyltransferase‐independent manner, through the inhibition of TBK1.

    • Gcn5/PCAF and Gcn5/PCAF‐mediated H3K9ac are largely dispensable for gene activation in fibroblasts.

    • Gcn5/PCAF repress IFNB production and innate immunity independent of HAT activity.

    • Gcn5 inhibits phosphorylation and activation of innate immune signaling kinase TBK1.

    • Gcn5/PCAF
    • H3K9ac
    • innate immune signaling
    • interferon‐β
    • TBK1
    • Received April 30, 2014.
    • Revision received September 2, 2014.
    • Accepted September 4, 2014.
    Qihuang Jin, Lenan Zhuang, Binbin Lai, Chaochen Wang, Wenqian Li, Brian Dolan, Yue Lu, Zhibin Wang, Keji Zhao, Weiqun Peng, Sharon Y R Dent, Kai Ge
  • Heterotrimeric G proteins control stem cell proliferation through CLAVATA signaling in Arabidopsis
    1. Takashi Ishida1,,
    2. Ryo Tabata1,,
    3. Masashi Yamada2,3,,
    4. Mitsuhiro Aida4,
    5. Kanako Mitsumasu1,
    6. Masayuki Fujiwara4,
    7. Katsushi Yamaguchi5,
    8. Shuji Shigenobu5,
    9. Masayuki Higuchi4,
    10. Hiroyuki Tsuji4,
    11. Ko Shimamoto4,
    12. Mitsuyasu Hasebe6,7,
    13. Hiroo Fukuda2 and
    14. Shinichiro Sawa*,1
    1. 1Graduate School of Science and Technology, Kumamoto University, Kumamoto, Japan
    2. 2Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan
    3. 3Department of Biology and Institute for Genome Science and Policy Center for Systems Biology, Duke University, Durham, NC, USA
    4. 4Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Japan
    5. 5Functional Genomics Facility, National Institute for Basic Biology, Okazaki, Japan
    6. 6Division of Evolutionary Biology, National Institute for Basic Biology, Okazaki, Japan
    7. 7School of Life Science, The Graduate University for Advanced Studies, Okazaki, Japan
    1. *Corresponding author. Tel: +81 96 342 3439; E‐mail: sawa{at}kumamoto-u.ac.jp
    1. These authors are contributed equally to this work

    This study shows that heterotrimeric G proteins modulate stem cell proliferation in the plant shoot apical meristem via CLAVATA signaling pathway and provides evidence that that CLV3 peptide receptor RPK2 is a novel G protein‐coupled receptor.

    Synopsis

    This study shows that heterotrimeric G proteins modulate stem cell proliferation in the plant shoot apical meristem via CLAVATA signaling pathway and provides evidence that that CLV3 peptide receptor RPK2 is a novel G protein‐coupled receptor.

    • Mutations in the G protein beta‐subunit1 (agb1) lead to an enlarged shoot apical meristem.

    • This phenotype is similar to that of CLAVATA mutants.

    • AGB1 and the CLV3 receptor RPK2 associate and synergistically regulate stem cell homeostasis.

    • Arabidopsis thaliana
    • heterotrimeric G protein
    • peptide hormone
    • RECEPTOR‐LIKE PROTEIN KINASE 2
    • stem cell homeostasis
    • Received February 21, 2014.
    • Revision received August 13, 2014.
    • Accepted August 14, 2014.
    Takashi Ishida, Ryo Tabata, Masashi Yamada, Mitsuhiro Aida, Kanako Mitsumasu, Masayuki Fujiwara, Katsushi Yamaguchi, Shuji Shigenobu, Masayuki Higuchi, Hiroyuki Tsuji, Ko Shimamoto, Mitsuyasu Hasebe, Hiroo Fukuda, Shinichiro Sawa
  • SET8 methyltransferase activity during the DNA double‐strand break response is required for recruitment of 53BP1
    1. Stanimir Dulev1,,
    2. Johnny Tkach1,,
    3. Sichun Lin1 and
    4. Nizar N Batada*,1,2
    1. 1Ontario Institute for Cancer Research, Toronto, ON, Canada
    2. 2Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
    1. *Corresponding author. Tel: +1 416 662 1539; Fax: +1 416 977 1118; E‐mail: nizar.batada{at}oicr.on.ca
    1. These authors contributed equally to the manuscript

    This study demonstrates that SET8 is actively recruited to DNA double‐strand breaks and that its methyltransferase activity is needed to recruit 53BP1. These activities are required for double strand break repair, primarily via the NHEJ pathway.

    Synopsis

    This study demonstrates that SET8 is actively recruited to DNA double‐strand breaks and that its methyltransferase activity is needed to recruit 53BP1. These activities are required for double strand break repair, primarily via the NHEJ pathway.

    • SET8 is recruited to DNA DSBs where its monomethyltransferase activity is required for the local increase of methylated H4K20 and the recruitment of 53BP1.

    • SET8 promotes NHEJ in reporter‐based assays and in class switch recombination.

    • The recruitment of SET8 to DSBs can be PCNA‐independent and is negatively regulated by HDACs.

    • 53BP1
    • DNA repair
    • H4K20
    • NHEJ
    • Pr‐SET7
    • SET8
    • Received August 8, 2014.
    • Revision received September 4, 2014.
    • Accepted September 5, 2014.

    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.

    Stanimir Dulev, Johnny Tkach, Sichun Lin, Nizar N Batada
  • Pleiotropic roles of Notch signaling in normal, malignant, and developmental hematopoiesis in the human
    1. Rahul Kushwah1,,
    2. Borhane Guezguez1,,
    3. Jung Bok Lee1,
    4. Claudia I Hopkins1 and
    5. Mickie Bhatia*,1,2
    1. 1McMaster Stem Cell and Cancer Research Institute (SCC‐RI), Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada
    2. 2Department of Biochemistry and Biomedical Sciences, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada
    1. *Corresponding author. E‐mail: mbhatia{at}mcmaster.ca
    1. These authors contributed equally to this work

    The Notch pathway regulates normal and malignant hematopoiesis. This review discusses recent developments in understanding the role of Notch in the human hematopoietic system with special emphasis on hematopoietic initiation from human pluripotent stem cells and regulation within the bone marrow.

    • hematopoiesis
    • human pluripotent stem cells
    • leukemia
    • Notch
    • Received March 27, 2014.
    • Revision received August 21, 2014.
    • Accepted August 27, 2014.
    Rahul Kushwah, Borhane Guezguez, Jung Bok Lee, Claudia I Hopkins, Mickie Bhatia
  • Ack kinase regulates CTP synthase filaments during Drosophila oogenesis
    1. Todd I Strochlic*,14,
    2. Kevin P Stavrides1,2,
    3. Sam V Thomas1,
    4. Emmanuelle Nicolas3,
    5. Alana M O'Reilly*,1,2 and
    6. Jeffrey R Peterson*,1
    1. 1Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA, USA
    2. 2Epigenetics and Progenitor Cells Keystone Program, Fox Chase Cancer Center, Philadelphia, PA, USA
    3. 3Genomics Core Facility, Fox Chase Cancer Center, Philadelphia, PA, USA
    4. 4Department of Biochemistry & Molecular Biology, Drexel University College of Medicine, Philadelphia, PA, USA
    1. * Corresponding author. Tel: +1 215 762 3664; E‐mail: Todd.Strochlic{at}drexelmed.edu

      Corresponding author. Tel: +1 215 214 1653; E‐mail: Alana.OReilly{at}fccc.edu

      Corresponding author. Tel: +1 215 728 3568; Fax: +1 215 728 3574; E‐mail: jeffrey.peterson{at}fccc.edu

    DAck kinase is shown to localize to CTP synthase (CTPS) filaments in germ cells of the Drosophila ovary. DAck catalytic activity is required for normal CTPS filament morphology and CTP‐dependent processes such as RNA production, plasma membrane integrity and fertility.

    Synopsis

    DAck kinase is shown to localize to CTP synthase (CTPS) filaments in germ cells of the Drosophila ovary. DAck catalytic activity is required for normal CTPS filament morphology and CTP‐dependent processes such as RNA production, plasma membrane integrity and fertility.

    • DAck localizes to cytoplasmic assemblies of the nucleotide biosynthetic enzyme CTPS.

    • Catalytically active CTPS localizes to filaments.

    • Flies deficient in DAck catalytic activity have morphologically abnormal CTPS filaments, reduced RNA levels, membrane phospholipid defects and reduced fertility.

    • Ack
    • CTP synthase
    • cytoophidia
    • Drosophila oogenesis
    • Received February 25, 2014.
    • Revision received August 11, 2014.
    • Accepted August 12, 2014.
    Todd I Strochlic, Kevin P Stavrides, Sam V Thomas, Emmanuelle Nicolas, Alana M O'Reilly, Jeffrey R Peterson
  • Direct interaction of actin filaments with F‐BAR protein pacsin2
    1. Julius Kostan1,,
    2. Ulrich Salzer1,2,,
    3. Albina Orlova3,
    4. Imre Törö114,
    5. Vesna Hodnik4,
    6. Yosuke Senju5,
    7. Juan Zou6,
    8. Claudia Schreiner1,
    9. Julia Steiner1,
    10. Jari Meriläinen7,
    11. Marko Nikki7,
    12. Ismo Virtanen8,,
    13. Oliviero Carugo1,9,
    14. Juri Rappsilber7,10,
    15. Pekka Lappalainen5,
    16. Veli‐Pekka Lehto7,
    17. Gregor Anderluh4,11,12,
    18. Edward H Egelman3 and
    19. Kristina Djinović‐Carugo*,1,13
    1. 1Department of Structural and Computational Biology, Max F. Perutz Laboratories, University of Vienna, Vienna, Austria
    2. 2Department of Medical Biochemistry, Medical University of Vienna, Vienna, Austria
    3. 3Department of Biochemistry and Molecular Genetics, University of Virginia Medical Center, Charlottesville, VA, USA
    4. 4Department of Biology, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia
    5. 5Program in Cell and Molecular Biology, Institute of Biotechnology, University of Helsinki, Helsinki, Finland
    6. 6Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, UK
    7. 7Department of Pathology, Haartman Institute, University of Helsinki, Helsinki, Finland
    8. 8Institute of Biomedicine/Anatomy, University of Helsinki, Helsinki, Finland
    9. 9Department of Chemistry, University of Pavia, Pavia, Italy
    10. 10Department of Biotechnology, Technological University of Berlin, Berlin, Germany
    11. 11National Institute of Chemistry, Ljubljana, Slovenia
    12. 12EN‐FIST Centre of Excellence, Ljubljana, Slovena
    13. 13Department of Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia
    14. 14 MSD Werthenstein Biopharma GmbH, Schachen, Swizerland
    1. *Corresponding author. Tel: +43 1 4277 52203; E‐mail: kristina.djinovic{at}univie.ac.at
    1. These authors contributed equally to the work

    Actin polymerization together with proteins that directly deform membranes, such as BAR domain‐containing proteins, have been implicated in regulation of membrane shape. This study shows that the F‐BAR domain of pacsin2 binds actin filaments using the same concave surface employed to bind to membranes.

    Synopsis

    Actin polymerization together with proteins that directly deform membranes, such as BAR domain‐containing proteins, have been implicated in regulation of membrane shape. This study shows that the F‐BAR domain of pacsin2 binds actin filaments using the same concave surface employed to bind to membranes.

    • Three‐dimensional reconstruction of F‐actin with bound pacsin2.

    • Biochemical, mutational and XL‐MS data support the binding mode and suggest competition between negatively charged liposomes and F‐actin for binding to pacsin2.

    • cryo‐electron microscopy
    • F‐BAR protein pacsin2
    • F‐actin binding
    • membrane sculpting
    • Received July 21, 2014.
    • Revision received August 10, 2014.
    • Accepted August 11, 2014.
    Julius Kostan, Ulrich Salzer, Albina Orlova, Imre Törö, Vesna Hodnik, Yosuke Senju, Juan Zou, Claudia Schreiner, Julia Steiner, Jari Meriläinen, Marko Nikki, Ismo Virtanen, Oliviero Carugo, Juri Rappsilber, Pekka Lappalainen, Veli‐Pekka Lehto, Gregor Anderluh, Edward H Egelman, Kristina Djinović‐Carugo
  • HDAC4 promotes Pax7‐dependent satellite cell activation and muscle regeneration
    1. Moon‐Chang Choi1,
    2. Soyoung Ryu1,
    3. Rui Hao1,
    4. Bin Wang1,
    5. Meghan Kapur1,
    6. Chen‐Ming Fan2 and
    7. Tso‐Pang Yao*,1
    1. 1Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA
    2. 2Department of Embryology, Carnegie Institution of Washington, Baltimore, MD, USA
    1. *Corresponding author. Tel: +1 919 613 8654; E‐mail: tsopang.yao{at}duke.edu

    HDAC4 is shown to promote damage‐induced satellite cell (SC) proliferation and muscle regeneration in vivo by stimulating Pax7 expression. It also prevents aberrant lipid accumulation and induction of the brown fat transcription factor Prdm16 in regenerating muscle.

    Synopsis

    HDAC4 is shown to promote damage‐induced satellite cell (SC) proliferation and muscle regeneration in vivo by stimulating Pax7 expression. It also prevents aberrant lipid accumulation and induction of the brown fat transcription factor Prdm16 in regenerating muscle.

    • Loss of HDAC4 in SCs reduces expression of Pax7 and its target genes, which in turns inhibits SC proliferation.

    • Knockdown of HDAC4‐regulated Lix1, a Pax7 target, decreases the proliferative rate of SCs.

    • HDAC4 inactivation in SCs leads to a prominent reduction of microRNA‐133 and concomitant increase in its target, Prdm16, a master regulator of brown adipogenesis.

    • HDAC4
    • muscle regeneration
    • Pax7
    • Received June 20, 2014.
    • Revision received August 12, 2014.
    • Accepted August 14, 2014.
    Moon‐Chang Choi, Soyoung Ryu, Rui Hao, Bin Wang, Meghan Kapur, Chen‐Ming Fan, Tso‐Pang Yao