Role of Ets-1 in transcriptional regulation of transferrin receptor and erythroid differentiation
| Autor: | Ugo Testa, Edvige Perrotti, Valentina Lulli, Lukas C. Kühn, Eliana M. Coccia, Rémy Moret, Ramona Ilari, Giovanna Marziali, Angela Battistini |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Cancer Research
Erythrocytes Transcription Genetic Cellular differentiation Molecular Sequence Data Transferrin receptor Biology Proto-Oncogene Protein c-ets-1 Transcription (biology) Proto-Oncogene Proteins hemic and lymphatic diseases Receptors Transferrin Gene expression Tumor Cells Cultured Genetics Transcriptional regulation Humans Promoter Regions Genetic Molecular Biology Transcription factor Cells Cultured Base Sequence Proto-Oncogene Proteins c-ets Cell Differentiation DNA Molecular biology AP-1 transcription factor Gene Expression Regulation Regulatory sequence Protein Binding Transcription Factors |
| Zdroj: | Oncogene. 21:7933-7944 |
| ISSN: | 1476-5594 0950-9232 |
| Popis: | High expression of transferrin receptor (TfR) on the membrane of erythroid cells accounts for the high level of iron required to sustain heme synthesis. Several studies indicate that during erythroid differentiation TfR expression is highly dependent on transcriptional regulation. In this study we characterized the minimal region able to confer transcriptional regulation during erythroid differentiation in Friend leukemia cells (FLC). This region of 120 bp, upstream the transcription start site, contains an overlapping consensus recognition sequence for AP1/CREB/ATF transcription factors and for proteins of the Ets family and a GC rich region. Here, we report that both the Ets and the Ap1/CRE like sites are essential for promoter activity during erythroid differentiation. We showed that Ets-1 binds to the EBS-TfR and its binding activity decreases in FLC induced to differentiate and during normal erythroid differentiation. Consistent with this, FLC constitutively expressing Ets-1 show a decrease in TfR gene expression, globin mRNA and hemoglobin synthesis. We conclude that Ets-1 binding activity is modulated during erythroid maturation and that a deregulated expression of this transcription factor interferes with terminal erythroid differentiation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|