Source:http://linkedlifedata.com/resource/pubmed/id/12538596
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
13
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pubmed:dateCreated |
2003-3-24
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pubmed:abstractText |
beta-Arrestin1 and beta-arrestin2 play a key role in the regulation of G protein-coupled receptor-mediated signaling, whereas the subcellular distribution of beta-arrestin1 and beta-arrestin2 has been shown to be quite different. In this study, we found that although both beta-arrestin1 and beta-arrestin2 are able to interact with ubiquitin-protein isopeptide ligase (E3) Mdm2, only expression of beta-arrestin2 leads to the relocalization of Mdm2 from the nucleus to the cytoplasm. Further study reveals that beta-arrestin2 but not beta-arrestin1 shuttles between the cytoplasm and nucleus in a leptomycin B-sensitive manner. A hydrophobic amino acid-rich region (VXXXFXXLXL) at the C terminus of beta-arrestin2 was further demonstrated to serve as a nuclear export signal responsible for the extranuclear localization of beta-arrestin2. In the corresponding region of beta-arrestin1, there is a single amino acid difference (Glu instead of Leu in beta-arrestin2), and mutation of Glu to Leu conferred to beta-arrestin1 similar subcellular distribution to that of beta-arrestin2. Moreover, data from a series of deletion mutations demonstrated that the N domain (residues 1-185) was indispensable for the nuclear localization of both beta-arrestins, and the results from a Val to Asp point mutation in the N domain also supported this notion. In addition, our data showed that nucleocytoplasmic shuttling of beta-arrestin2 was required, via protein/protein interaction, for the cytoplasmic relocalization of Mdm2 and JNK3, another well known beta-arrestin2-binding protein. Our study thus suggests that both the nuclear export signal motif and the N domain of beta-arrestins are critical for the regulation of their subcellular localization and that beta-arrestin2 may modulate the function of its binding partners such as Mdm2 and JNK3 by alteration of their subcellular distribution.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
28
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
11648-53
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12538596-Active Transport, Cell Nucleus,
pubmed-meshheading:12538596-Amino Acid Sequence,
pubmed-meshheading:12538596-Animals,
pubmed-meshheading:12538596-Arrestins,
pubmed-meshheading:12538596-Blotting, Western,
pubmed-meshheading:12538596-Cytoplasm,
pubmed-meshheading:12538596-Humans,
pubmed-meshheading:12538596-Molecular Sequence Data,
pubmed-meshheading:12538596-Sequence Homology, Amino Acid,
pubmed-meshheading:12538596-Subcellular Fractions,
pubmed-meshheading:12538596-Tumor Cells, Cultured
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pubmed:year |
2003
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pubmed:articleTitle |
Subcellular localization of beta-arrestins is determined by their intact N domain and the nuclear export signal at the C terminus.
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pubmed:affiliation |
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, People's Republic of China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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