| Leishmania Repression of Host Translation through mTOR Cleavage Is Required for Parasite Survival and Infection. | |
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MedLine Citation:
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PMID: 21501832 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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The protozoan parasite Leishmania alters the activity of its host cell, the macrophage. However, little is known about the effect of Leishmania infection on host protein synthesis. Here, we show that the Leishmania protease GP63 cleaves the mammalian/mechanistic target of rapamycin (mTOR), a serine/threonine kinase that regulates the translational repressor 4E-BP1. mTOR cleavage results in the inhibition of mTOR complex 1 (mTORC1) and concomitant activation of 4E-BP1 to promote Leishmania proliferation. Consistent with these results, pharmacological activation of 4E-BPs with rapamycin, results in a dramatic increase in parasite replication. In contrast, genetic deletion of 4E-BP1/2 reduces parasite load in macrophages ex vivo and decreases susceptibility to cutaneous leishmaniasis in vivo. The parasite resistant phenotype of 4E-BP1/2 double-knockout mice involves an enhanced type I IFN response. This study demonstrates that Leishmania evolved a survival mechanism by activating 4E-BPs, which serve as major targets for host translational control. |
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Authors:
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Maritza Jaramillo; Maria Adelaida Gomez; Ola Larsson; Marina Tiemi Shio; Ivan Topisirovic; Irazú Contreras; Randi Luxenburg; Amy Rosenfeld; Rodney Colina; Robert W McMaster; Martin Olivier; Mauro Costa-Mattioli; Nahum Sonenberg |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Cell host & microbe Volume: 9 ISSN: 1934-6069 ISO Abbreviation: Cell Host Microbe Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-04-19 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101302316 Medline TA: Cell Host Microbe Country: United States |
Other Details:
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Languages: eng Pagination: 331-41 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Biochemistry and Goodman Cancer Center, McGill University, Montreal, Quebec H3G 1Y6, Canada. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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