Document Detail


Identification of a nuclear localization sequence in β-arrestin-1 and its functional implications.
MedLine Citation:
PMID:  22267743     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A 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 post-translational modification profile of p65/RelA. Further mutational analysis identified Lys(157) within the putative NLS as being critical to nuclear localization of β-arrestin-1. Substitution of Lys(157) 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.
Authors:
Crystal Zoe Hoeppner; Ni Cheng; Richard D Ye
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-01-21
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-03-19     Completed Date:  2012-06-12     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  8932-43     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, College of Medicine, University of Illinois, Chicago, Illinois 60612, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Arrestins / chemistry*,  genetics,  metabolism*
Cell Nucleus / chemistry,  genetics,  metabolism*
HeLa Cells
Humans
Molecular Sequence Data
Nuclear Localization Signals*
Protein Transport
Grant Support
ID/Acronym/Agency:
AI033503/AI/NIAID NIH HHS; AI040176/AI/NIAID NIH HHS; HL077806/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Arrestins; 0/Nuclear Localization Signals; 0/beta-arrestin
Comments/Corrections

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