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A Reporter Screen in a Human Haploid Cell Line Identifies CYLD as a Constitutive Inhibitor of NF-κB

The development of forward genetic screens in human haploid cells has the potential to transform our understanding of the genetic basis of cellular processes unique to man. So far, this approach has been limited mostly to the identification of genes that mediate cell death in response to a lethal ag...

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Autores principales: Lee, Clarissa C., Carette, Jan E., Brummelkamp, Thijn R., Ploegh, Hidde L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3704534/
https://www.ncbi.nlm.nih.gov/pubmed/23861985
http://dx.doi.org/10.1371/journal.pone.0070339
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author Lee, Clarissa C.
Carette, Jan E.
Brummelkamp, Thijn R.
Ploegh, Hidde L.
author_facet Lee, Clarissa C.
Carette, Jan E.
Brummelkamp, Thijn R.
Ploegh, Hidde L.
author_sort Lee, Clarissa C.
collection PubMed
description The development of forward genetic screens in human haploid cells has the potential to transform our understanding of the genetic basis of cellular processes unique to man. So far, this approach has been limited mostly to the identification of genes that mediate cell death in response to a lethal agent, likely due to the ease with which this phenotype can be observed. Here, we perform the first reporter screen in the near-haploid KBM7 cell line to identify constitutive inhibitors of NF-κB. CYLD was the only currently known negative regulator of NF-κB to be identified, thus uniquely distinguishing this gene. Also identified were three genes with no previous known connection to NF-κB. Our results demonstrate that reporter screens in haploid human cells can be applied to investigate the many complex signaling pathways that converge upon transcription factors.
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spelling pubmed-37045342013-07-16 A Reporter Screen in a Human Haploid Cell Line Identifies CYLD as a Constitutive Inhibitor of NF-κB Lee, Clarissa C. Carette, Jan E. Brummelkamp, Thijn R. Ploegh, Hidde L. PLoS One Research Article The development of forward genetic screens in human haploid cells has the potential to transform our understanding of the genetic basis of cellular processes unique to man. So far, this approach has been limited mostly to the identification of genes that mediate cell death in response to a lethal agent, likely due to the ease with which this phenotype can be observed. Here, we perform the first reporter screen in the near-haploid KBM7 cell line to identify constitutive inhibitors of NF-κB. CYLD was the only currently known negative regulator of NF-κB to be identified, thus uniquely distinguishing this gene. Also identified were three genes with no previous known connection to NF-κB. Our results demonstrate that reporter screens in haploid human cells can be applied to investigate the many complex signaling pathways that converge upon transcription factors. Public Library of Science 2013-07-08 /pmc/articles/PMC3704534/ /pubmed/23861985 http://dx.doi.org/10.1371/journal.pone.0070339 Text en © 2013 Lee et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Lee, Clarissa C.
Carette, Jan E.
Brummelkamp, Thijn R.
Ploegh, Hidde L.
A Reporter Screen in a Human Haploid Cell Line Identifies CYLD as a Constitutive Inhibitor of NF-κB
title A Reporter Screen in a Human Haploid Cell Line Identifies CYLD as a Constitutive Inhibitor of NF-κB
title_full A Reporter Screen in a Human Haploid Cell Line Identifies CYLD as a Constitutive Inhibitor of NF-κB
title_fullStr A Reporter Screen in a Human Haploid Cell Line Identifies CYLD as a Constitutive Inhibitor of NF-κB
title_full_unstemmed A Reporter Screen in a Human Haploid Cell Line Identifies CYLD as a Constitutive Inhibitor of NF-κB
title_short A Reporter Screen in a Human Haploid Cell Line Identifies CYLD as a Constitutive Inhibitor of NF-κB
title_sort reporter screen in a human haploid cell line identifies cyld as a constitutive inhibitor of nf-κb
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3704534/
https://www.ncbi.nlm.nih.gov/pubmed/23861985
http://dx.doi.org/10.1371/journal.pone.0070339
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