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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
1996-9-5
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pubmed:abstractText |
The mi locus of mice encodes a member of the basic-helix-loop-helix-leucine zipper (bHLH-Zip) protein family of transcription factors (hereafter called MITF). Cultured mast cells of mi/mi genotype (mi/mi CMCs) did not normally respond to stem cell factor (SCF), a ligand for the c-kit receptor tyrosine kinase. The poor response of mi/mi CMCs to SCF was attributed to the deficient expression of c-kit both the mRNA and protein levels. The purpose of the present study is to investigate the effect of MITF on the transcription of the c-kit gene. First, we introduced cDNA encoding normal (+) MITF or mutant (mi) MITF into mi/mi CMCs using the retroviral vector. Overexpression of (+)-MITF but not mi-MITF normalized the expression of the c-kit and the poor response of mi/mi CMCs to SCF, indicating the involvement of (+)-MITF in the c-kit gene transactivation. Second, we analyzed the promoter of the c-kit gene. Three CANNTG motifs recognized by bHLH-Zip-type transcription factors were conserved between the mouse and human c-kit promoters. Among these three CANNTG motifs, only the CACCTG motif (nt -356 to -351) was specifically bound by (+)-MITF. When the luciferase gene under the control of the c-kit promoter was contransfected into NIH/3T3 fibroblasts with cDNA encoding (+)-MITF or mi-MITF, the luciferase activity significantly increased only when (+)-MITF cDNA was cotransfected. The deletion of the promoter region containing the CACCTG motif or the mutation of the CACCTG to CTCCAG abolished the transactivation effect of (+)-MITF, indicating that (+)-MITF transactivated the c-kit gene through the CACCTG motif. When the luciferase gene under the control of the c-kit promoter was introduced into the FMA3 mastocytoma and FEC-P1 myeloid cell lines, remarkable luciferase activity was observed only in FMA3 cells. Thus, the involvement of (+)-MITF in the c-kit transactivation appeared to be specific to the mast cell lineage.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/MITF protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Microphthalmia-Associated...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitf protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-kit,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0006-4971
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
88
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1225-33
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:8695840-Animals,
pubmed-meshheading:8695840-Base Sequence,
pubmed-meshheading:8695840-Cells, Cultured,
pubmed-meshheading:8695840-DNA Primers,
pubmed-meshheading:8695840-DNA-Binding Proteins,
pubmed-meshheading:8695840-Gene Expression Regulation,
pubmed-meshheading:8695840-Helix-Loop-Helix Motifs,
pubmed-meshheading:8695840-Humans,
pubmed-meshheading:8695840-Leucine Zippers,
pubmed-meshheading:8695840-Mast Cells,
pubmed-meshheading:8695840-Mice,
pubmed-meshheading:8695840-Mice, Mutant Strains,
pubmed-meshheading:8695840-Microphthalmia-Associated Transcription Factor,
pubmed-meshheading:8695840-Molecular Sequence Data,
pubmed-meshheading:8695840-Promoter Regions, Genetic,
pubmed-meshheading:8695840-Proto-Oncogene Proteins c-kit,
pubmed-meshheading:8695840-RNA, Messenger,
pubmed-meshheading:8695840-Sequence Alignment,
pubmed-meshheading:8695840-Sequence Homology, Nucleic Acid,
pubmed-meshheading:8695840-Transcription Factors,
pubmed-meshheading:8695840-Transcriptional Activation
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pubmed:year |
1996
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pubmed:articleTitle |
Involvement of transcription factor encoded by the mi locus in the expression of c-kit receptor tyrosine kinase in cultured mast cells of mice.
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pubmed:affiliation |
Department of Pathology, Medical School, Osaka University, Suita, Japan.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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