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
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
2011 Impact Factor: 4.773
2011 SCImago Journal Rankings: 0.793
DOIhttp://dx.doi.org/10.1074/jbc.M602556200
ISI Accession Number IDWOS:000239702900062
ReferencesReferences in Scopus
DC Field
Value
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
dc.identifier.epage23879
dc.identifier.hkuros129021
dc.identifier.isiWOS:000239702900062
dc.identifier.issn0021-9258
2011 Impact Factor: 4.773
2011 SCImago Journal Rankings: 0.793
dc.identifier.issue33
dc.identifier.openurl
dc.identifier.pmid16782704
dc.identifier.scopuseid_2-s2.0-33747701560
dc.identifier.spage23870
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
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