Topoisomerase 1 inhibition suppresses inflammatory genes and protects from death by inflammation-Reference-Cited by-同舟云学术

Topoisomerase 1 inhibition suppresses inflammatory genes and protects from death by inflammation

Published:2016-05-27 Issue:6289 Volume:352 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Rialdi Alex¹²,Campisi Laura¹²,Zhao Nan¹²,Lagda Arvin Cesar¹²,Pietzsch Colette³,Ho Jessica Sook Yuin⁴,Martinez-Gil Luis¹⁵,Fenouil Romain⁶,Chen Xiaoting⁷,Edwards Megan¹,Metreveli Giorgi¹²,Jordan Stefan⁸,Peralta Zuleyma⁶,Munoz-Fontela Cesar⁹,Bouvier Nicole¹,Merad Miriam⁸,Jin Jian¹⁰,Weirauch Matthew⁷,Heinz Sven¹¹¹²,Benner Chris¹²,van Bakel Harm⁶,Basler Christopher¹,García-Sastre Adolfo¹²,Bukreyev Alexander³,Marazzi Ivan¹²

Affiliation:

1. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

2. Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

3. Department of Pathology, Microbiology, and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.

4. Laboratory of Methyltransferases in Development and Disease, Institute of Molecular and Cell Biology, Singapore.

5. Department of Biochemistry and Molecular Biology, Universitat de Valencia, Valencia, Spain.

6. Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

7. Center for Autoimmune Genomics and Etiology (CAGE) and Divisions of Biomedical Informatics and Developmental Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.

8. Department of Oncological Sciences, Tisch Cancer Institute and Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

9. Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.

10. Department of Structural and Chemical Biology, Department of Oncological Sciences, and Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

11. Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.

12. Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.

Abstract

Unwinding DNA and unleasing inflammation Fighting infections often comes with collateral damage, which sometimes can be deadly. For instance, in septic shock, the overwhelming release of inflammatory mediators drives multi-organ failure. Rialdi et al. now report a potential new therapeutic target for controlling excessive inflammation: the DNA unwinding enzyme topoisomerase I (Top1) (see the Perspective by Pope and Medzhitov). Upon infection, Top1 specifically localizes to the promoters of pathogen-induced genes and promotes their transcription by helping to recruit RNA polymerase II. Pharmacological inhibition of Top1 in a therapeutic setting increased survival in several mouse models of severe microbially induced inflammation. Science , this issue p. 10.1126/science.aad7993 ; see also p. 1058

Funder

National Institute of Allergy and Infectious Diseases

Public Health Service Institutional Research

Department of Defense

NIH

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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