Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1996-9-5
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
88
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1225-33
pubmed:dateRevised
2009-11-19
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
pubmed:year
1996
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.
pubmed:affiliation
Department of Pathology, Medical School, Osaka University, Suita, Japan.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't