Positive and Negative Regulation of the Master Metabolic Regulator mTORC1 by Two Families of Legionella pneumophila Effectors.
Autor: | De Leon JA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA., Qiu J; Purdue Institute for Inflammation, Immunology, and Infectious Disease and Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA., Nicolai CJ; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA., Counihan JL; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA., Barry KC; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA., Xu L; Purdue Institute for Inflammation, Immunology, and Infectious Disease and Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA., Lawrence RE; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA., Castellano BM; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA., Zoncu R; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA., Nomura DK; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA., Luo ZQ; Purdue Institute for Inflammation, Immunology, and Infectious Disease and Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA. Electronic address: luoz@purdue.edu., Vance RE; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: rvance@berkeley.edu. |
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Jazyk: | angličtina |
Zdroj: | Cell reports [Cell Rep] 2017 Nov 21; Vol. 21 (8), pp. 2031-2038. |
DOI: | 10.1016/j.celrep.2017.10.088 |
Abstrakt: | All pathogens must acquire nutrients from their hosts. The intracellular bacterial pathogen Legionella pneumophila, the etiological agent of Legionnaires' disease, requires host amino acids for growth within cells. The mechanistic target of rapamycin complex 1 (mTORC1) is an evolutionarily conserved master regulator of host amino acid metabolism. Here, we identify two families of translocated L. pneumophila effector proteins that exhibit opposing effects on mTORC1 activity. The Legionella glucosyltransferase (Lgt) effector family activates mTORC1, through inhibition of host translation, whereas the SidE/SdeABC (SidE) effector family acts as mTORC1 inhibitors. We demonstrate that a common activity of both effector families is to inhibit host translation. We propose that the Lgt and SidE families of effectors work in concert to liberate host amino acids for consumption by L. pneumophila. (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.) |
Databáze: | MEDLINE |
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