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  • Regulation of G6PD acetylation by KAT9/SIRT2 modulates NADPH homeostasis and cell survival during oxidative stress
    1. Yi‐Ping Wang1,
    2. Li‐Sha Zhou1,
    3. Yu‐Zheng Zhao2,
    4. Shi‐Wen Wang1,
    5. Lei‐Lei Chen1,
    6. Li‐Xia Liu3,
    7. Zhi‐Qiang Ling4,
    8. Fu‐Jun Hu5,
    9. Yi‐Ping Sun1,
    10. Jing‐Ye Zhang1,
    11. Chen Yang3,
    12. Yi Yang2,
    13. Yue Xiong1,6,
    14. Kun‐Liang Guan1,7 and
    15. Dan Ye*,1
    1. 1Key Laboratory of Molecular Medicine of Ministry of Education and Institutes of Biomedical Sciences, Shanghai Medical College College of Life Science Fudan University, Shanghai, China
    2. 2School of Pharmacy East China University of Science and Technology, Shanghai, China
    3. 3Key Laboratory of Synthetic Biology, Bioinformatics Center and Laboratory of Systems Biology, Institute of Plant Physiology and Ecology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences, Shanghai, China
    4. 4Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital Zhejiang Cancer Center, Hangzhou, China
    5. 5Department of Radiotherapy, Zhejiang Province Cancer Hospital Zhejiang Cancer Center, Hangzhou, China
    6. 6Lineberger Comprehensive Cancer Center, Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, USA
    7. 7Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, CA, USA
    1. *Corresponding author. Tel: +86 21 5423 7834; Fax: +86 21 5423 7450; E‐mail: yedan{at}fudan.edu.cn

    Following oxidative stress, production of the reductant NADPH via the pentose phosphate pathway is stimulated by SIRT2‐mediated deacetylation and activation of G6PD.

    Synopsis

    The pentose phosphate pathway plays an important role in the oxidative stress response by supplying the reductant NADPH. SIRT2‐mediated deacetylation and activation of the glucose‐6‐phosphate dehydrogenase, the rate‐limiting enzyme in this pathway, stimulates the production of cytosolic NADPH to counteract oxidative damage.

    • K403 acetylation decreases G6PD activity by inhibiting dimer formation.

    • SIRT2 and KAT9/ELP3 regulate G6PD K403 acetylation.

    • Regulation of G6PD K403 acetylation modulates NADPH homeostasis and cell survival during oxidative stress.

    • acetylation
    • G6PD
    • nicotinamide adenine dinucleotide phosphate
    • reactive oxygen species
    • SIRT2
    • Received October 23, 2013.
    • Revision received January 25, 2014.
    • Accepted March 18, 2014.
    Yi‐Ping Wang, Li‐Sha Zhou, Yu‐Zheng Zhao, Shi‐Wen Wang, Lei‐Lei Chen, Li‐Xia Liu, Zhi‐Qiang Ling, Fu‐Jun Hu, Yi‐Ping Sun, Jing‐Ye Zhang, Chen Yang, Yi Yang, Yue Xiong, Kun‐Liang Guan, Dan Ye
  • Synapse reorganization—a new partnership revealed
    1. Takeo Saneyoshi1 and
    2. Yasunori Hayashi (yhayashi{at}brain.riken.jp) 1,2
    1. 1Brain Science Institute RIKEN, Wako, Saitama, Japan
    2. 2Saitama University Brain Science Institute Saitama University, Saitama, Japan

    Changes in synaptic function require both qualitative and quantitative reorganization of the synaptic components. Ca2+ plays a central role in this process, but the mechanism has not been fully elucidated. Zhang et al report a novel mechanism whereby Ca2+/calmodulin (CaM) regulates the stability of the postsynaptic scaffold. Ca2+/CaM interacts with PSD‐95, a core protein in the postsynaptic density (PSD) that supports synaptic signaling and structural components. Ca2+/CaM interferes with the palmitoylation of PSD‐95, resulting in the dissociation of PSD‐95 from the postsynaptic membrane. This process may explain the reduction of surface glutamate receptor observed during synaptic depression and homeostatic regulation of the synaptic response after prolonged neuronal activity.

    See also: Y Zhang et al

    New findings reveal that calcium and calmodulin affect the stability of the postsynaptic scaffold by regulating palmitoylation and synaptic membrane localization of PSD‐95.

    Takeo Saneyoshi, Yasunori Hayashi
  • Key regulators control distinct transcriptional programmes in blood progenitor and mast cells
    1. Fernando J Calero‐Nieto*,1,,
    2. Felicia S Ng1,,
    3. Nicola K Wilson1,
    4. Rebecca Hannah1,
    5. Victoria Moignard1,
    6. Ana I Leal‐Cervantes1,
    7. Isabel Jimenez‐Madrid1,
    8. Evangelia Diamanti1,
    9. Lorenz Wernisch2 and
    10. Berthold Göttgens*,1
    1. 1Department of Haematology, Wellcome Trust and MRC Cambridge Stem Cell Institute, Cambridge Institute for Medical Research, Cambridge University, Cambridge, UK
    2. 2MRC Biostatistics Unit, Institute of Public Health, Cambridge, UK
    1. * Corresponding author. Tel: +44 1223 336822; Fax: +44 1223 762670; E‐mail: fjc28{at}cam.ac.uk

      Corresponding author. Tel: +44 1223 336829; Fax: +44 1223 762670; E‐mail: bg200{at}cam.ac.uk

    1. These authors contributed equally to this work.

    Comparative profiling of ten key haematopoietic transcription factors in blood progenitors versus mast cells demonstrates tissue‐specific binding profiles that functionally determine cellular identify.

    Synopsis

    Comparative profiling of ten key haematopoietic transcription factors in blood progenitors versus mast cells demonstrates tissue‐specific binding profiles that functionally determine cellular identify.

    • Genome‐wide binding profiles for 10 TFs in blood progenitors and mast cells

    • Differential binding of shared TFs is predictive of differential gene expression.

    • Cell type‐specific TFs may reorganise global binding profiles of shared TFs.

    • Cell type‐specific binding of shared TFs is not predominantly opportunistic.

    • gene regulation
    • haematopoiesis
    • mast cells
    • progenitors
    • Received September 6, 2013.
    • Revision received February 27, 2014.
    • Accepted March 20, 2014.

    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.

    Fernando J Calero‐Nieto, Felicia S Ng, Nicola K Wilson, Rebecca Hannah, Victoria Moignard, Ana I Leal‐Cervantes, Isabel Jimenez‐Madrid, Evangelia Diamanti, Lorenz Wernisch, Berthold Göttgens
  • Dendritic cell maturation: functional specialization through signaling specificity and transcriptional programming
    1. Marc Dalod1,2,3,,
    2. Rabie Chelbi1,2,3,
    3. Bernard Malissen1,2,3, and
    4. Toby Lawrence*,1,2,3,
    1. 1Centre d'Immunologie de Marseille‐Luminy (CIML), Aix‐Marseille University UM2, Marseille, France
    2. 2Institut National de la Santé et de la Recherche Médicale (INSERM) U1104, Marseille, France
    3. 3Centre National de la Recherche Scientifique (CNRS), UMR7280, Marseille, France
    1. *Corresponding author. Tel: +33 491269166; Fax: +33 491269430; E‐mail: lawrence{at}ciml.univ-mrs.fr
    1. Senior authors sharing equal contribution.

    Toby Lawrence and colleagues review the characteristics of Dendritic Cell (DC) subsets in the immune system and discuss the complex processes leading to DC functional maturation during steady‐state and inflammatory conditions.

    • dendritic cells
    • homeostasis
    • immunity
    • tolerance
    • Received January 27, 2014.
    • Revision received March 17, 2014.
    • Accepted March 19, 2014.
    Marc Dalod, Rabie Chelbi, Bernard Malissen, Toby Lawrence
  • Coordination of transposon expression with DNA replication in the targeting of telomeric retrotransposons in Drosophila
    1. Liang Zhang1,
    2. Michelle Beaucher1,,
    3. Yan Cheng1, and
    4. Yikang S Rong*,1
    1. 1Laboratory of Biochemistry and Molecular Biology, National Cancer Institute (NCI) NIH, Bethesda, MD, USA
    1. *Corresponding author. Tel: +1 301 451 8335; Fax: +1 301 435 3697; E‐mail: rongy{at}mail.nih.gov
    1. Equal contribution.

    Telomerase‐independent maintenance of Drosophila telomeres via retrotransposon elements involves telomere targeting of ribonucleoprotein structures and coincides with telomere replication, revealing parallels with telomerase‐mediated mechanisms in other species.

    Synopsis

    Telomerase‐independent maintenance of Drosophila telomeres via retrotransposon elements is here shown to involve telomere targeting of ribonucleoprotein structures, in a process that coincides with telomere replication and requires the homolog of a key telomeric protein from telomerase‐dependent species.

    • HeT‐A retrotransposon‐encoded Orf1p protein is produced predominantly in (early) S‐phase cells.

    • Orf1p assembles large, spherical ribonucleoprotein structures (“HeT‐A spheres”) at telomeres.

    • HeT‐A sphere telomere recruitment and telomere replication happen in a similar time window.

    • HeT‐A sphere attachment to telomeres depends on the putative Stn1 homolog Verrocchio.

    • CST complex
    • Drosophila telomere
    • telomere replication
    • telomeric transposon
    • Received September 19, 2013.
    • Revision received March 17, 2014.
    • Accepted March 20, 2014.
    Liang Zhang, Michelle Beaucher, Yan Cheng, Yikang S Rong
  • Crystal structures of the structure‐selective nuclease Mus81‐Eme1 bound to flap DNA substrates
    1. Gwang Hyeon Gwon1,
    2. Aera Jo1,
    3. Kyuwon Baek1,
    4. Kyeong Sik Jin2,
    5. Yaoyao Fu1,
    6. Jong‐Bong Lee3,
    7. YoungChang Kim4 and
    8. Yunje Cho*,1
    1. 1Department of Life Science, Pohang University of Science and Technology, Pohang, South Korea
    2. 2Pohang Accelerator Laboratory, Pohang University of Science and Technology, Pohang, South Korea
    3. 3Department of Physics, Pohang University of Science and Technology, Pohang, South Korea
    4. 4Biosciences Division, Structural Biology Center Argonne National Laboratory, Argonne, IL, USA
    1. *Corresponding author. Tel: +82 54 279 2288; Fax: +82 54 279 8111; E‐mail: yunje{at}postech.ac.kr

    Co‐crystallization of human Mus81‐Eme1 bound to flap DNA substrates reveals key structural features essential for substrate selection and active site positioning during resolution of recombination intermediates.

    Synopsis

    The structure‐selective nuclease Mus81‐Eme1 plays key roles in resolving recombination intermediates such as in the repair of DNA interstrand cross‐links. Co‐crystallization of the human enzyme bound to flap DNA substrates reveals key structural features essential for substrate selection and active site positioning of the incision strand.

    • Mus81‐Eme1 undergoes a structural transition from a closed state to an open state in response to a DNA binding.

    • A specific “5′ end binding pocket” hosts the nicked junction 5′ end of post‐nick duplex DNA.

    • A hydrophobic wedge separates pre‐ and post‐nick duplex and facilitates bending of a nicked substrate.

    • Mus81‐Eme1 shares key structural features with 5′ flap nucleases, but with opposite substrate recognition chirality.

    • crystal structure
    • flap DNA
    • homologous recombination
    • interstrand cross‐link repair
    • Mus81
    • Received January 3, 2014.
    • Revision received March 12, 2014.
    • Accepted March 18, 2014.
    Gwang Hyeon Gwon, Aera Jo, Kyuwon Baek, Kyeong Sik Jin, Yaoyao Fu, Jong‐Bong Lee, YoungChang Kim, Yunje Cho
  • Epigenetic memory: the Lamarckian brain
    1. Andre Fischer*,1,2
    1. 1Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany
    2. 2German Center for Neurodegenerative Diseases (DZNE) Goettigen Site, Göttingen, Germany
    1. *Corresponding author. Tel: +49 5513910378; Fax: +49 551399836; E‐mail: afische2{at}gwdg.de

    As part of our review series on Molecular Memory, Andre Fischer discusses epigenetic processes leading to memory formation and transgenerational inheritance under physiological and pathological conditions such as Alzheimer's disease.

    • Alzheimer's disease
    • epigenetics
    • histone‐acetylation
    • memory
    • neurodegeneration
    • non‐coding RNA
    • Received December 10, 2013.
    • Revision received January 9, 2014.
    • Accepted January 13, 2014.

    This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs 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.

    Andre Fischer