Source:http://linkedlifedata.com/resource/pubmed/id/18215124
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2008-4-22
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pubmed:abstractText |
NF1 (nuclear factor 1) binds to two upstream elements of the human ANT2 (adenine nucleotide translocator-2) promoter and actively represses expression of the gene in growth-arrested diploid skin fibroblasts [Luciakova, Barath, Poliakova, Persson and Nelson (2003) J. Biol. Chem. 278, 30624-30633]. ChIP (chromatin immunoprecipitation) and co-immunoprecipitation analyses of nuclear extracts from growth-arrested and growth-activated diploid cells demonstrate that NF1, when acting as a repressor, is part of a multimeric complex that also includes Smad and Sp-family proteins. This complex appears to be anchored to both the upstream NF1-repressor elements and the proximal promoter, Sp1-dependent activation elements in growth-arrested cells. In growth-activated cells, the repressor complex dissociates and NF1 leaves the promoter. As revealed by co-immunoprecipitation experiments, NF1-Smad4-Sp3 complexes are present in nuclear extracts only from growth-inhibited cells, suggesting that the growth-state-dependent formation of these complexes is not an ANT2 promoter-specific event. Consistent with the role of Smad proteins in the repression complex, TGF-beta (transforming growth factor-beta) can fully repress ANT2 transcription in normally growing fibroblasts. Finally, pull-down experiments of in vitro transcribed/translated NF1 isoforms by GST (glutathione transferase)-Smad and GST-Smad MH fusion proteins indicate direct physical interactions between members of the two families. These findings suggest a possible functional relationship between the NF1 and Smad proteins that has not been previously observed.
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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/Adenine Nucleotide Translocator 2,
http://linkedlifedata.com/resource/pubmed/chemical/Culture Media, Serum-Free,
http://linkedlifedata.com/resource/pubmed/chemical/Multiprotein Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/Neurofibromin 1,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Smad Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Sp Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1470-8728
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
412
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
123-30
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:18215124-Adenine Nucleotide Translocator 2,
pubmed-meshheading:18215124-Cell Proliferation,
pubmed-meshheading:18215124-Cells, Cultured,
pubmed-meshheading:18215124-Culture Media, Serum-Free,
pubmed-meshheading:18215124-Down-Regulation,
pubmed-meshheading:18215124-Humans,
pubmed-meshheading:18215124-Models, Biological,
pubmed-meshheading:18215124-Multigene Family,
pubmed-meshheading:18215124-Multiprotein Complexes,
pubmed-meshheading:18215124-Neurofibromin 1,
pubmed-meshheading:18215124-Promoter Regions, Genetic,
pubmed-meshheading:18215124-Protein Binding,
pubmed-meshheading:18215124-Repressor Proteins,
pubmed-meshheading:18215124-Smad Proteins,
pubmed-meshheading:18215124-Sp Transcription Factors,
pubmed-meshheading:18215124-Transcription, Genetic
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pubmed:year |
2008
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pubmed:articleTitle |
Growth-dependent repression of human adenine nucleotide translocator-2 (ANT2) transcription: evidence for the participation of Smad and Sp family proteins in the NF1-dependent repressor complex.
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pubmed:affiliation |
Cancer Research Institute, Slovak Academy of Sciences, Vlarska 7, 83391 Bratislava, Slovak Republic. Katarina.Luciakova@savba.sk
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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