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Article: Regulation of nucleocytoplasmic trafficking of transcription factor OREBP/TonEBP/NFAT5
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TitleRegulation of nucleocytoplasmic trafficking of transcription factor OREBP/TonEBP/NFAT5
 
AuthorsTong, EHY1 2
Guo, JJ1 2 4
Huang, AL4
Liu, H3
Hu, CD3
Chung, SSM1 1
Ko, BCB1 2
 
Issue Date2006
 
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
 
CitationJournal Of Biological Chemistry, 2006, v. 281 n. 33, p. 23870-23879 [How to Cite?]
DOI: http://dx.doi.org/10.1074/jbc.M602556200
 
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.
 
ISSN0021-9258
2012 Impact Factor: 4.651
2012 SCImago Journal Rankings: 2.723
 
DOIhttp://dx.doi.org/10.1074/jbc.M602556200
 
ISI Accession Number IDWOS:000239702900062
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorTong, EHY
 
dc.contributor.authorGuo, JJ
 
dc.contributor.authorHuang, AL
 
dc.contributor.authorLiu, H
 
dc.contributor.authorHu, CD
 
dc.contributor.authorChung, SSM
 
dc.contributor.authorKo, BCB
 
dc.date.accessioned2010-09-06T08:14:14Z
 
dc.date.available2010-09-06T08:14:14Z
 
dc.date.issued2006
 
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.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationJournal Of Biological Chemistry, 2006, v. 281 n. 33, p. 23870-23879 [How to Cite?]
DOI: http://dx.doi.org/10.1074/jbc.M602556200
 
dc.identifier.doihttp://dx.doi.org/10.1074/jbc.M602556200
 
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2012 Impact Factor: 4.651
2012 SCImago Journal Rankings: 2.723
 
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dc.identifier.urihttp://hdl.handle.net/10722/81136
 
dc.identifier.volume281
 
dc.languageeng
 
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
 
dc.publisher.placeUnited States
 
dc.relation.ispartofJournal of Biological Chemistry
 
dc.relation.referencesReferences in Scopus
 
dc.rightsJournal of Biological Chemistry. Copyright © American Society for Biochemistry and Molecular Biology, Inc.
 
dc.titleRegulation of nucleocytoplasmic trafficking of transcription factor OREBP/TonEBP/NFAT5
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong
  2. Institute of Molecular Technology for Drug Discovery and Synthesis, Hong Kong
  3. Purdue University
  4. Chongqing University of Medical Sciences