Transcription Factor SCL Is Required for c-kit Expression and c-Kit Function in Hemopoietic Cells
| العنوان: | Transcription Factor SCL Is Required for c-kit Expression and c-Kit Function in Hemopoietic Cells |
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| المؤلفون: | Mona Nemer, Frédéric Charron, Martin Lefrancois, Paul-Henri Roméo, Ilan R. Kirsch, Gang He, Trang Hoang, Gorazd Krosl, Paul Jolicoeur |
| المصدر: | Scopus-Elsevier ResearcherID The Journal of Experimental Medicine |
| بيانات النشر: | Rockefeller University Press, 1998. |
| سنة النشر: | 1998 |
| مصطلحات موضوعية: | animal structures, Cell Survival, Immunology, Gene Expression, Bone Marrow Cells, Stem cell factor, Biology, behavioral disciplines and activities, immune system diseases, Proto-Oncogene Proteins, hemic and lymphatic diseases, Basic Helix-Loop-Helix Transcription Factors, Tumor Cells, Cultured, Humans, Immunology and Allergy, Transcription factor, T-Cell Acute Lymphocytic Leukemia Protein 1, Interleukin 3, Stem Cell Factor, TAL1, fungi, apoptosis, Granulocyte-Macrophage Colony-Stimulating Factor, Articles, Oligonucleotides, Antisense, Molecular biology, DNA-Binding Proteins, Proto-Oncogene Proteins c-kit, Haematopoiesis, Steel factor, c-kit, Cell culture, Apoptosis, SCL, Interleukin-3, Ectopic expression, Transcription Factors |
| الوصف: | In normal hemopoietic cells that are dependent on specific growth factors for cell survival, the expression of the basic helix-loop-helix transcription factor SCL/Tal1 correlates with that of c-Kit, the receptor for Steel factor (SF) or stem cell factor. To address the possibility that SCL may function upstream of c-kit, we sought to modulate endogenous SCL function in the CD34+ hemopoietic cell line TF-1, which requires SF, granulocyte/macrophage colony–stimulating factor, or interleukin 3 for survival. Ectopic expression of an antisense SCL cDNA (as-SCL) or a dominant negative SCL (dn-SCL) in these cells impaired SCL DNA binding activity, and prevented the suppression of apoptosis by SF only, indicating that SCL is required for c-Kit–dependent cell survival. Consistent with the lack of response to SF, the level of c-kit mRNA and c-Kit protein was significantly and specifically reduced in as-SCL– or dn-SCL– expressing cells. c-kit mRNA, c-kit promoter activity, and the response to SF were rescued by SCL overexpression in the antisense or dn-SCL transfectants. Furthermore, ectopic c-kit expression in as-SCL transfectants is sufficient to restore cell survival in response to SF. Finally, enforced SCL in the pro–B cell line Ba/F3, which is both SCL and c-kit negative is sufficient to induce c-Kit and SF responsiveness. Together, these results indicate that c-kit, a gene that is essential for the survival of primitive hemopoietic cells, is a downstream target of the transcription factor SCL. |
| تدمد: | 1540-9538 0022-1007 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::18623dfa7c1b55cf5991722ee4846f72Test https://doi.org/10.1084/jem.188.3.439Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....18623dfa7c1b55cf5991722ee4846f72 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15409538 00221007 |
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