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Article: Regulation of nucleocytoplasmic trafficking of transcription factor OREBP/TonEBP/NFAT5

TitleRegulation of nucleocytoplasmic trafficking of transcription factor OREBP/TonEBP/NFAT5
Authors
Issue Date2006
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal Of Biological Chemistry, 2006, v. 281 n. 33, p. 23870-23879 How to Cite?
AbstractThe osmotic response element-binding protein (OREBP), also known as tonicity enhancer-binding protein (TonEBP) or NFAT5, regulates the hypertonicity-induced expression of a battery of genes crucial for the adaptation of mammalian cells to extracellular hypertonic stress. The activity of OREBP/TonEBP is regulated at multiple levels, including nucleocytoplasmic trafficking. OREBP/TonEBP protein can be detected in both the cytoplasm and nucleus under isotonic conditions, although it accumulates exclusively in the nucleus or cytoplasm when subjected to hypertonic or hypotonic challenges, respectively. Using immunocytochemistry and green fluorescent protein fusions, the protein domains that determine its subcellular localization were identified and characterized. We found that OREBP/TonEBP nuclear import is regulated by a nuclear localization signal. However, under isotonic conditions, nuclear export of OREBP/TonEBP is mediated by a CRM1-dependent, leucine-rich canonical nuclear export sequence (NES) located in the N terminus. Disruption of NES by site-directed mutagenesis yielded a mutant OREBP/TonEBP protein that accumulated in the nucleus under isotonic conditions but remained a target for hypotonicity-induced nuclear export. More importantly, a putative auxiliary export domain distal to the NES was identified. Disruption of the auxiliary export domain alone is sufficient to abolish the nuclear export of OREBP/TonEBP induced by hypotonicity. By using bimolecular fluorescence complementation assay, we showed that CRM1 interacts with OREBP/TonEBP, but not with a mutant protein deficient in NES. Our findings provide insight into how nucleocytoplasmic trafficking of OREBP/TonEBP is regulated by changes in extracellular tonicity. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/81136
ISSN
2020 Impact Factor: 5.157
2023 SCImago Journal Rankings: 1.766
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorTong, EHYen_HK
dc.contributor.authorGuo, JJen_HK
dc.contributor.authorHuang, ALen_HK
dc.contributor.authorLiu, Hen_HK
dc.contributor.authorHu, CDen_HK
dc.contributor.authorChung, SSMen_HK
dc.contributor.authorKo, BCBen_HK
dc.date.accessioned2010-09-06T08:14:14Z-
dc.date.available2010-09-06T08:14:14Z-
dc.date.issued2006en_HK
dc.identifier.citationJournal Of Biological Chemistry, 2006, v. 281 n. 33, p. 23870-23879en_HK
dc.identifier.issn0021-9258en_HK
dc.identifier.urihttp://hdl.handle.net/10722/81136-
dc.description.abstractThe osmotic response element-binding protein (OREBP), also known as tonicity enhancer-binding protein (TonEBP) or NFAT5, regulates the hypertonicity-induced expression of a battery of genes crucial for the adaptation of mammalian cells to extracellular hypertonic stress. The activity of OREBP/TonEBP is regulated at multiple levels, including nucleocytoplasmic trafficking. OREBP/TonEBP protein can be detected in both the cytoplasm and nucleus under isotonic conditions, although it accumulates exclusively in the nucleus or cytoplasm when subjected to hypertonic or hypotonic challenges, respectively. Using immunocytochemistry and green fluorescent protein fusions, the protein domains that determine its subcellular localization were identified and characterized. We found that OREBP/TonEBP nuclear import is regulated by a nuclear localization signal. However, under isotonic conditions, nuclear export of OREBP/TonEBP is mediated by a CRM1-dependent, leucine-rich canonical nuclear export sequence (NES) located in the N terminus. Disruption of NES by site-directed mutagenesis yielded a mutant OREBP/TonEBP protein that accumulated in the nucleus under isotonic conditions but remained a target for hypotonicity-induced nuclear export. More importantly, a putative auxiliary export domain distal to the NES was identified. Disruption of the auxiliary export domain alone is sufficient to abolish the nuclear export of OREBP/TonEBP induced by hypotonicity. By using bimolecular fluorescence complementation assay, we showed that CRM1 interacts with OREBP/TonEBP, but not with a mutant protein deficient in NES. Our findings provide insight into how nucleocytoplasmic trafficking of OREBP/TonEBP is regulated by changes in extracellular tonicity. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.en_HK
dc.languageengen_HK
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_HK
dc.relation.ispartofJournal of Biological Chemistryen_HK
dc.rightsJournal of Biological Chemistry. Copyright © American Society for Biochemistry and Molecular Biology, Inc.en_HK
dc.titleRegulation of nucleocytoplasmic trafficking of transcription factor OREBP/TonEBP/NFAT5en_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0021-9258&volume=281&spage=23870&epage=23879&date=2006&atitle=Regulation+of+nucleocytoplasmic+trafficking+of+transcription+factor+OREBP/TonEBP/NFAT5en_HK
dc.identifier.emailChung, SSM: smchung@hkucc.hku.hken_HK
dc.identifier.authorityChung, SSM=rp00376en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1074/jbc.M602556200en_HK
dc.identifier.pmid16782704-
dc.identifier.scopuseid_2-s2.0-33747701560en_HK
dc.identifier.hkuros129021en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33747701560&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume281en_HK
dc.identifier.issue33en_HK
dc.identifier.spage23870en_HK
dc.identifier.epage23879en_HK
dc.identifier.isiWOS:000239702900062-
dc.publisher.placeUnited Statesen_HK
dc.identifier.f10001161002-
dc.identifier.scopusauthoridTong, EHY=7006335224en_HK
dc.identifier.scopusauthoridGuo, JJ=23766904300en_HK
dc.identifier.scopusauthoridHuang, AL=7402307198en_HK
dc.identifier.scopusauthoridLiu, H=7409757546en_HK
dc.identifier.scopusauthoridHu, CD=7404565695en_HK
dc.identifier.scopusauthoridChung, SSM=14120761600en_HK
dc.identifier.scopusauthoridKo, BCB=7102833927en_HK
dc.identifier.issnl0021-9258-

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