v-Jun downregulates the alpha 2 (I) collagen target gene indirectly through Sp1/3
| Autor: | Marc Castellazzi, Sandrine Chamboredon |
|---|---|
| Přispěvatelé: | Virologie humaine, École normale supérieure de Lyon (ENS de Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Castellazzi, Marc |
| Rok vydání: | 2005 |
| Předmět: |
Cancer Research
Sp1 Transcription Factor Molecular Sequence Data Extracellular matrix component Oncogene Protein p65(gag-jun) CAAT box Down-Regulation Sp3 alpha 2 (I) collagen cell transformation Chick Embryo [SDV.GEN] Life Sciences [q-bio]/Genetics Biology Collagen Type I Sp1 chemistry.chemical_compound Downregulation and upregulation Genetics medicine Animals Promoter Regions Genetic Fibroblast Molecular Biology Psychological repression Transcription factor Gene Oligonucleotide Array Sequence Analysis v-Jun [SDV.GEN]Life Sciences [q-bio]/Genetics Base Sequence primary chick embryo fibroblasts Fibroblasts Molecular biology DNA-Binding Proteins Sp3 Transcription Factor medicine.anatomical_structure chemistry Drosophila Collagen DNA Transcription Factors |
| Zdroj: | Oncogene Oncogene, 2005, 24, pp.2547-2557 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1208489 |
| Popis: | Transformation of chick embryo fibroblasts (CEFs) by the v-Jun oncoprotein correlates with a downregulation of the alpha 2 (I) collagen gene. To investigate whether this gene constitutes a direct target of v-Jun, an analysis of a large proximal fragment of the promoter, extending from position -1080 to +109, was performed. Transient transfections with -1080/+109 and deleted derivatives revealed that a short proximal fragment, -433/+11, is the target for repression by v-Jun. Extensive analysis, conducted in CEFs and in Sp1/3-deficient Drosophila SL2 cells, further showed that (i) high constitutive activity of -433/+11 requires a direct binding of the ubiquitous Sp1 and/or Sp3 transcription factors acting on two distinct motifs, that is, a proximal TCC-rich region and an upstream GC box, and that (ii) repression by v-Jun does not require any direct binding of the oncoprotein to the DNA, but an indirect binding within a v-Jun-Sp1/3-DNA chromatin-associated complex. This situation is reminiscent of a situation previously reported with the tata-less, SPARC (secreted protein, acidic, and rich in cysteine) target promoter that regulates the expression of another extracellular matrix component in the same model of cell transformation. Taken together, these data reinforce the view that, at least in CEFs, v-Jun downregulates a family of direct target genes by binding to the DNA indirectly through Sp1/3. |
| Databáze: | OpenAIRE |
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