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­­­Silencing of retrotransposons by SETDB1 inhibits the interferon response in acute myeloid leukemia­­

A propensity for rewiring genetic and epigenetic regulatory networks, thus enabling sustained cell proliferation, suppression of apoptosis, and the ability to evade the immune system, is vital to cancer cell propagation. An increased understanding of how this is achieved is critical for identifying...

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Autores principales: Cuellar, Trinna L., Herzner, Anna-Maria, Zhang, Xiaotian, Goyal, Yogesh, Watanabe, Colin, Friedman, Brad A., Janakiraman, Vasantharajan, Durinck, Steffen, Stinson, Jeremy, Arnott, David, Cheung, Tommy K., Chaudhuri, Subhra, Modrusan, Zora, Doerr, Jonas Martin, Classon, Marie, Haley, Benjamin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5674883/
https://www.ncbi.nlm.nih.gov/pubmed/28887438
http://dx.doi.org/10.1083/jcb.201612160
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author Cuellar, Trinna L.
Herzner, Anna-Maria
Zhang, Xiaotian
Goyal, Yogesh
Watanabe, Colin
Friedman, Brad A.
Janakiraman, Vasantharajan
Durinck, Steffen
Stinson, Jeremy
Arnott, David
Cheung, Tommy K.
Chaudhuri, Subhra
Modrusan, Zora
Doerr, Jonas Martin
Classon, Marie
Haley, Benjamin
author_facet Cuellar, Trinna L.
Herzner, Anna-Maria
Zhang, Xiaotian
Goyal, Yogesh
Watanabe, Colin
Friedman, Brad A.
Janakiraman, Vasantharajan
Durinck, Steffen
Stinson, Jeremy
Arnott, David
Cheung, Tommy K.
Chaudhuri, Subhra
Modrusan, Zora
Doerr, Jonas Martin
Classon, Marie
Haley, Benjamin
author_sort Cuellar, Trinna L.
collection PubMed
description A propensity for rewiring genetic and epigenetic regulatory networks, thus enabling sustained cell proliferation, suppression of apoptosis, and the ability to evade the immune system, is vital to cancer cell propagation. An increased understanding of how this is achieved is critical for identifying or improving therapeutic interventions. In this study, using acute myeloid leukemia (AML) human cell lines and a custom CRISPR/Cas9 screening platform, we identify the H3K9 methyltransferase SETDB1 as a novel, negative regulator of innate immunity. SETDB1 is overexpressed in many cancers, and loss of this gene in AML cells triggers desilencing of retrotransposable elements that leads to the production of double-stranded RNAs (dsRNAs). This is coincident with induction of a type I interferon response and apoptosis through the dsRNA-sensing pathway. Collectively, our findings establish a unique gene regulatory axis that cancer cells can exploit to circumvent the immune system.
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spelling pubmed-56748832018-05-06 ­­­Silencing of retrotransposons by SETDB1 inhibits the interferon response in acute myeloid leukemia­­ Cuellar, Trinna L. Herzner, Anna-Maria Zhang, Xiaotian Goyal, Yogesh Watanabe, Colin Friedman, Brad A. Janakiraman, Vasantharajan Durinck, Steffen Stinson, Jeremy Arnott, David Cheung, Tommy K. Chaudhuri, Subhra Modrusan, Zora Doerr, Jonas Martin Classon, Marie Haley, Benjamin J Cell Biol Research Articles A propensity for rewiring genetic and epigenetic regulatory networks, thus enabling sustained cell proliferation, suppression of apoptosis, and the ability to evade the immune system, is vital to cancer cell propagation. An increased understanding of how this is achieved is critical for identifying or improving therapeutic interventions. In this study, using acute myeloid leukemia (AML) human cell lines and a custom CRISPR/Cas9 screening platform, we identify the H3K9 methyltransferase SETDB1 as a novel, negative regulator of innate immunity. SETDB1 is overexpressed in many cancers, and loss of this gene in AML cells triggers desilencing of retrotransposable elements that leads to the production of double-stranded RNAs (dsRNAs). This is coincident with induction of a type I interferon response and apoptosis through the dsRNA-sensing pathway. Collectively, our findings establish a unique gene regulatory axis that cancer cells can exploit to circumvent the immune system. The Rockefeller University Press 2017-11-06 /pmc/articles/PMC5674883/ /pubmed/28887438 http://dx.doi.org/10.1083/jcb.201612160 Text en © 2017 Cuellar et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Cuellar, Trinna L.
Herzner, Anna-Maria
Zhang, Xiaotian
Goyal, Yogesh
Watanabe, Colin
Friedman, Brad A.
Janakiraman, Vasantharajan
Durinck, Steffen
Stinson, Jeremy
Arnott, David
Cheung, Tommy K.
Chaudhuri, Subhra
Modrusan, Zora
Doerr, Jonas Martin
Classon, Marie
Haley, Benjamin
­­­Silencing of retrotransposons by SETDB1 inhibits the interferon response in acute myeloid leukemia­­
title ­­­Silencing of retrotransposons by SETDB1 inhibits the interferon response in acute myeloid leukemia­­
title_full ­­­Silencing of retrotransposons by SETDB1 inhibits the interferon response in acute myeloid leukemia­­
title_fullStr ­­­Silencing of retrotransposons by SETDB1 inhibits the interferon response in acute myeloid leukemia­­
title_full_unstemmed ­­­Silencing of retrotransposons by SETDB1 inhibits the interferon response in acute myeloid leukemia­­
title_short ­­­Silencing of retrotransposons by SETDB1 inhibits the interferon response in acute myeloid leukemia­­
title_sort ­­­silencing of retrotransposons by setdb1 inhibits the interferon response in acute myeloid leukemia­­
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5674883/
https://www.ncbi.nlm.nih.gov/pubmed/28887438
http://dx.doi.org/10.1083/jcb.201612160
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