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Identification of a nuclear localization sequence in β-arrestin-1 and its functional implications
Hoeppner C.Z.1; Cheng N.1; Ye R.D.1
2012-03-16
Source PublicationJournal of Biological Chemistry
ISSN00219258 1083351X
Volume287Issue:12Pages:8932-8943
AbstractA mounting body of evidence suggests that β-arrestin-1 plays important roles in the nucleus, but how β-arrestin-1 enters the nucleus remains unclear because no nuclear import signal has been identified in the β-arrestins. We sought to characterize the cellular localization of wild type β-arrestin-1 and a series of N domain mutants to determine the structural basis and functional implications of β-arrestin-1 nuclear localization. A seven-residue candidate nuclear localization sequence (NLS) was identified based on sequence analysis. Mutation of the NLS led to a loss of β-arrestin-1 nuclear localization in transfected cells. Exogenous expression of wild type β-arrestin-1 enhanced the transcriptional activity of nuclear factor κB (NF-κB) induced by bradykinin, whereas mutation of the NLS reduced this effect by two-thirds relative to wild type controls. Loss of β-arrestin-1 nuclear localization was accompanied by reduced recruitment of the CREB-binding protein and altered posttranslational modification profile of p65/RelA. Further mutational analysis identified Lys within the putative NLS as being critical to nuclear localization of β-arrestin-1. Substitution of Lys to Ala led to reduced nuclear localization, decreased promoter binding by p65/RelA and decreased IL-1β gene transcription. These results demonstrate a critical role for β-arrestin-1 nuclear localization in scaffolding and transcriptional regulation. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
DOI10.1074/jbc.M111.294058
URLView the original
Language英語
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Cited Times [WOS]:21   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.University of Illinois College of Medicine
2.Shanghai Jiao Tong University
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GB/T 7714
Hoeppner C.Z.,Cheng N.,Ye R.D.. Identification of a nuclear localization sequence in β-arrestin-1 and its functional implications[J]. Journal of Biological Chemistry,2012,287(12):8932-8943.
APA Hoeppner C.Z.,Cheng N.,&Ye R.D..(2012).Identification of a nuclear localization sequence in β-arrestin-1 and its functional implications.Journal of Biological Chemistry,287(12),8932-8943.
MLA Hoeppner C.Z.,et al."Identification of a nuclear localization sequence in β-arrestin-1 and its functional implications".Journal of Biological Chemistry 287.12(2012):8932-8943.
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