Regulation of the MAD1 promoter by G-CSF
العنوان: | Regulation of the MAD1 promoter by G-CSF |
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المؤلفون: | Bernhard Lüscher, Juliane Lüscher-Firzlaff, Kan Jiang, Kolja Eckert, Nadine Hein |
المصدر: | Nucleic Acids Research |
بيانات النشر: | Oxford University Press (OUP), 2008. |
سنة النشر: | 2008 |
مصطلحات موضوعية: | STAT3 Transcription Factor, Transcriptional Activation, MAPK/ERK pathway, TATA box, Molecular Sequence Data, Repressor, Biology, Response Elements, Cell Line, Mice, Genes, Reporter, Sequence Homology, Nucleic Acid, Granulocyte Colony-Stimulating Factor, Genetics, Transcriptional regulation, Animals, Humans, Promoter Regions, Genetic, Molecular Biology, Base Sequence, Ccaat-enhancer-binding proteins, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Promoter, Molecular biology, Chromatin, Rats, Repressor Proteins, Receptors, Granulocyte Colony-Stimulating Factor, CCAAT-Enhancer-Binding Proteins, Signal transduction, Signal Transduction |
الوصف: | MAD family proteins are transcriptional repressors that antagonize the functions of MYC oncoproteins. In particular, MAD1 has been demonstrated to interfere with MYC-induced proliferation, transformation and apoptosis. The MAD1 gene is expressed in distinct patterns, mainly associated with differentiation and quiescence. We observed that MAD1 is directly activated by G-CSF in promyelocytic cell lines. To investigate the transcriptional regulation of the human MAD1 gene, we have cloned and characterized its promoter. A region of high homology between the MAD1 orthologs of human, mouse and rat contains the core promoter, marked by open chromatin, high GC content and the lack of a TATA box. Using deletion constructs we identified two CCAAT-boxes occupied by C/EBPalpha and beta in the homology region that mediate responsiveness to G-CSF receptor signaling. The necessary signals include the activation of STAT3 and the RAS/RAF/ERK pathway. STAT3 does not bind directly to promoter DNA, but is recruited by C/EBPbeta. In summary, our studies provide a first analysis of the MAD1 promoter and suggest STAT3 functions as a C/EBPbeta cofactor in the regulation of the MAD1 gene. Our findings provide the base for the characterization of additional signal transduction pathways that control the expression of MAD1. |
تدمد: | 1362-4962 0305-1048 |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::945c31f27418d92c204182940965905dTest https://doi.org/10.1093/nar/gkn002Test |
حقوق: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....945c31f27418d92c204182940965905d |
قاعدة البيانات: | OpenAIRE |
تدمد: | 13624962 03051048 |
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