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Article: The kinase LRRK2 is a regulator of the transcription factor NFAT that modulates the severity of inflammatory bowel disease
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TitleThe kinase LRRK2 is a regulator of the transcription factor NFAT that modulates the severity of inflammatory bowel disease
 
AuthorsLiu, Z2
Lee, J2
Krummey, S2
Lu, W2
Cai, H1
Lenardo, MJ2
 
Issue Date2011
 
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/ni
 
CitationNature Immunology, 2011, v. 12 n. 11, p. 1063-1070 [How to Cite?]
DOI: http://dx.doi.org/10.1038/ni.2113
 
AbstractLeucine-rich repeat kinase 2 (LRRK2) has been identified by genome-wide association studies as being encoded by a major susceptibility gene for Crohn's disease. Here we found that LRRK2 deficiency conferred enhanced susceptibility to experimental colitis in mice. Mechanistic studies showed that LRRK2 was a potent negative regulator of the transcription factor NFAT and was a component of a complex that included the large noncoding RNA NRON (an NFAT repressor). Furthermore, the risk-associated allele encoding LRRK2 Met2397 identified by a genome-wide association study for Crohn's disease resulted in less LRRK2 protein post-translationally. Severe colitis in LRRK2-deficient mice was associated with enhanced nuclear localization of NFAT1. Thus, our study defines a new step in the control of NFAT activation that involves an immunoregulatory function of LRRK2 and has important implications for inflammatory bowel disease. © 2011 Nature America, Inc. All rights reserved.
 
ISSN1529-2908
2012 Impact Factor: 26.199
2012 SCImago Journal Rankings: 14.933
 
DOIhttp://dx.doi.org/10.1038/ni.2113
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorLiu, Z
 
dc.contributor.authorLee, J
 
dc.contributor.authorKrummey, S
 
dc.contributor.authorLu, W
 
dc.contributor.authorCai, H
 
dc.contributor.authorLenardo, MJ
 
dc.date.accessioned2012-10-08T03:20:58Z
 
dc.date.available2012-10-08T03:20:58Z
 
dc.date.issued2011
 
dc.description.abstractLeucine-rich repeat kinase 2 (LRRK2) has been identified by genome-wide association studies as being encoded by a major susceptibility gene for Crohn's disease. Here we found that LRRK2 deficiency conferred enhanced susceptibility to experimental colitis in mice. Mechanistic studies showed that LRRK2 was a potent negative regulator of the transcription factor NFAT and was a component of a complex that included the large noncoding RNA NRON (an NFAT repressor). Furthermore, the risk-associated allele encoding LRRK2 Met2397 identified by a genome-wide association study for Crohn's disease resulted in less LRRK2 protein post-translationally. Severe colitis in LRRK2-deficient mice was associated with enhanced nuclear localization of NFAT1. Thus, our study defines a new step in the control of NFAT activation that involves an immunoregulatory function of LRRK2 and has important implications for inflammatory bowel disease. © 2011 Nature America, Inc. All rights reserved.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationNature Immunology, 2011, v. 12 n. 11, p. 1063-1070 [How to Cite?]
DOI: http://dx.doi.org/10.1038/ni.2113
 
dc.identifier.citeulike9895048
 
dc.identifier.doihttp://dx.doi.org/10.1038/ni.2113
 
dc.identifier.epage1070
 
dc.identifier.issn1529-2908
2012 Impact Factor: 26.199
2012 SCImago Journal Rankings: 14.933
 
dc.identifier.issue11
 
dc.identifier.pmid21983832
 
dc.identifier.scopuseid_2-s2.0-80054933395
 
dc.identifier.spage1063
 
dc.identifier.urihttp://hdl.handle.net/10722/168577
 
dc.identifier.volume12
 
dc.languageeng
 
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/ni
 
dc.publisher.placeUnited States
 
dc.relation.ispartofNature Immunology
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshActive Transport, Cell Nucleus
 
dc.subject.meshAnimals
 
dc.subject.meshCell Line
 
dc.subject.meshCell Nucleus - Metabolism
 
dc.subject.meshColitis - Chemically Induced - Genetics - Immunology - Metabolism
 
dc.subject.meshCrohn Disease - Genetics
 
dc.subject.meshDisease Models, Animal
 
dc.subject.meshGenetic Predisposition To Disease
 
dc.subject.meshHumans
 
dc.subject.meshMacrophage Activation - Genetics
 
dc.subject.meshMice
 
dc.subject.meshMice, Inbred C57bl
 
dc.subject.meshMice, Knockout
 
dc.subject.meshNfatc Transcription Factors - Metabolism
 
dc.subject.meshProtein Processing, Post-Translational - Immunology
 
dc.subject.meshProtein-Serine-Threonine Kinases - Genetics - Metabolism
 
dc.subject.meshRna, Untranslated - Metabolism
 
dc.subject.meshTransgenes - Genetics
 
dc.titleThe kinase LRRK2 is a regulator of the transcription factor NFAT that modulates the severity of inflammatory bowel disease
 
dc.typeArticle
 
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Author Affiliations
  1. National Institute on Aging
  2. National Institute of Allergy and Infectious Diseases