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Article: The kinase LRRK2 is a regulator of the transcription factor NFAT that modulates the severity of inflammatory bowel disease

TitleThe kinase LRRK2 is a regulator of the transcription factor NFAT that modulates the severity of inflammatory bowel disease
Authors
Issue Date2011
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/ni
Citation
Nature Immunology, 2011, v. 12 n. 11, p. 1063-1070 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/168577
ISSN
2014 Impact Factor: 20.004
2014 SCImago Journal Rankings: 13.722
References

 

DC FieldValueLanguage
dc.contributor.authorLiu, Zen_US
dc.contributor.authorLee, Jen_US
dc.contributor.authorKrummey, Sen_US
dc.contributor.authorLu, Wen_US
dc.contributor.authorCai, Hen_US
dc.contributor.authorLenardo, MJen_US
dc.date.accessioned2012-10-08T03:20:58Z-
dc.date.available2012-10-08T03:20:58Z-
dc.date.issued2011en_US
dc.identifier.citationNature Immunology, 2011, v. 12 n. 11, p. 1063-1070en_US
dc.identifier.issn1529-2908en_US
dc.identifier.urihttp://hdl.handle.net/10722/168577-
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.en_US
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/nien_US
dc.relation.ispartofNature Immunologyen_US
dc.subject.meshActive Transport, Cell Nucleusen_US
dc.subject.meshAnimalsen_US
dc.subject.meshCell Lineen_US
dc.subject.meshCell Nucleus - Metabolismen_US
dc.subject.meshColitis - Chemically Induced - Genetics - Immunology - Metabolismen_US
dc.subject.meshCrohn Disease - Geneticsen_US
dc.subject.meshDisease Models, Animalen_US
dc.subject.meshGenetic Predisposition To Diseaseen_US
dc.subject.meshHumansen_US
dc.subject.meshMacrophage Activation - Geneticsen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Inbred C57blen_US
dc.subject.meshMice, Knockouten_US
dc.subject.meshNfatc Transcription Factors - Metabolismen_US
dc.subject.meshProtein Processing, Post-Translational - Immunologyen_US
dc.subject.meshProtein-Serine-Threonine Kinases - Genetics - Metabolismen_US
dc.subject.meshRna, Untranslated - Metabolismen_US
dc.subject.meshTransgenes - Geneticsen_US
dc.titleThe kinase LRRK2 is a regulator of the transcription factor NFAT that modulates the severity of inflammatory bowel diseaseen_US
dc.typeArticleen_US
dc.identifier.emailLu, W:luwei@hku.hken_US
dc.identifier.authorityLu, W=rp00754en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/ni.2113en_US
dc.identifier.pmid21983832en_US
dc.identifier.scopuseid_2-s2.0-80054933395en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-80054933395&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume12en_US
dc.identifier.issue11en_US
dc.identifier.spage1063en_US
dc.identifier.epage1070en_US
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridLiu, Z=54391368500en_US
dc.identifier.scopusauthoridLee, J=54391152600en_US
dc.identifier.scopusauthoridKrummey, S=21735094800en_US
dc.identifier.scopusauthoridLu, W=27868087600en_US
dc.identifier.scopusauthoridCai, H=7202853130en_US
dc.identifier.scopusauthoridLenardo, MJ=7005933199en_US
dc.identifier.citeulike9895048-

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