Source:http://linkedlifedata.com/resource/pubmed/id/21439937
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2011-4-25
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pubmed:abstractText |
In order to activate gene expression, transcription factors such as c-Jun have to reside in the nucleus. The abundance of c-Jun in the nucleus correlates with the activity of its target genes. As a consequence of excessive c-Jun activation, cells undergo apoptosis or changes in differentiation whereas decreased c-Jun function can reduce proliferation. In the present study we addressed how nuclear accumulation of the transcription factor c-Jun is regulated. First, we analyzed which functions of c-Jun are required for efficient nuclear accumulation. Mutants of c-Jun deficient in dimerization or DNA-binding show no defect in nuclear transport. Furthermore, c-Jun import into the nucleus of living cells occurred when the c-Jun phosphorylation sites were mutated as well in cells that lack the major c-Jun kinase, JNK, suggesting that c-Jun transport into the nucleus does not require JNK signaling. Conversely, however, binding of c-Jun seemed to enhance nuclear accumulation of JNK. In order to identify proteins that might be relevant for the nuclear translocation of c-Jun we searched for novel binding partners by a proteomic approach. In addition to the heat shock protein HSP70 and the DNA damage repair factors Ku70 and 80, we isolated human importin 8 as a novel interactor of c-Jun. Interaction of Imp 8 with c-Jun in human cells was confirmed by co-immunoprecipitation experiments. Nuclear accumulation of c-Jun does not require its functions as a transcription factor or the interaction with its kinase JNK. Interestingly, nuclear accumulation of JNK is regulated by interaction with c-Jun. Unraveling the mechanisms of c-Jun and JNK transport to the nucleus and its regulation will improve our understanding of their role in biological and pathophysiological processes.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/IPO8 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ku autoantigen,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 4,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-jun,
http://linkedlifedata.com/resource/pubmed/chemical/beta Karyopherins
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1090-2104
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pubmed:author | |
pubmed:copyrightInfo |
Copyright © 2011 Elsevier Inc. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
22
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pubmed:volume |
407
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
735-40
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pubmed:meshHeading |
pubmed-meshheading:21439937-Antigens, Nuclear,
pubmed-meshheading:21439937-Cell Nucleus,
pubmed-meshheading:21439937-DNA-Binding Proteins,
pubmed-meshheading:21439937-HEK293 Cells,
pubmed-meshheading:21439937-Humans,
pubmed-meshheading:21439937-MAP Kinase Kinase 4,
pubmed-meshheading:21439937-Phosphorylation,
pubmed-meshheading:21439937-Protein Structure, Tertiary,
pubmed-meshheading:21439937-Proto-Oncogene Proteins c-jun,
pubmed-meshheading:21439937-beta Karyopherins
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pubmed:year |
2011
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pubmed:articleTitle |
c-Jun localizes to the nucleus independent of its phosphorylation by and interaction with JNK and vice versa promotes nuclear accumulation of JNK.
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pubmed:affiliation |
Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Campus North, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany.
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pubmed:publicationType |
Journal Article
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