C/EBPβ is a MYB- and p300-cooperating pro-leukemogenic factor and promising drug target in acute myeloid leukemia
| العنوان: | C/EBPβ is a MYB- and p300-cooperating pro-leukemogenic factor and promising drug target in acute myeloid leukemia |
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| المؤلفون: | Amke Trentmann, Debora A. Casolari, Maria V. Yusenko, Henning D. Mootz, Jan-Henrik Mikesch, Karl-Heinz Klempnauer, Mairin Lenz, Maria Francisca Arteaga, Richard J D'Andrea, Wolfgang Dörner, Stefan Klempnauer, Thomas J. Schmidt, Luca Abdel Ghani, Melanie Horn, Carsten Müller-Tidow, Thomas J. Gonda |
| المساهمون: | Yusenko, Maria V, Trentmann, Amke, Casolari, Debora A, Abdel Ghani, Luca, Lenz, Mairin, Horn, Melanie, Dörner, Wolfgang, Klempnauer, Stefan, Mootz, Henning D, Arteaga, Maria Francisca, Mikesch, Jan Henrik, D'Andrea, Richard J, Gonda, Thomas J, Müller-Tidow, Carsten, Schmidt, Thomas J, Klempnauer, Karl Heinz |
| المصدر: | Oncogene |
| بيانات النشر: | Nature Publishing Group UK, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Biology, drug target, Article, Acute myeloid leukaemia, 03 medical and health sciences, 0302 clinical medicine, acute myeloid leukemia (AML), Genetics, MYB, Progenitor cell, Molecular Biology, Transcription factor, Gene, Cell growth, CCAAT-Enhancer-Binding Protein-beta, Myeloid leukemia, Cell Differentiation, MYB activity, Haematopoiesis, Leukemia, Myeloid, Acute, 030104 developmental biology, Mechanisms of disease, 030220 oncology & carcinogenesis, Cancer research, Transcription factor MYB, Ectopic expression |
| الوصف: | Transcription factor MYB has recently emerged as a promising drug target for the treatment of acute myeloid leukemia (AML). Here, we have characterized a group of natural sesquiterpene lactones (STLs), previously shown to suppress MYB activity, for their potential to decrease AML cell proliferation. Unlike what was initially thought, these compounds inhibit MYB indirectly via its cooperation partner C/EBPβ. C/EBPβ-inhibitory STLs affect the expression of a large number of MYB-regulated genes, suggesting that the cooperation of MYB and C/EBPβ broadly shapes the transcriptional program of AML cells. We show that expression of GFI1, a direct MYB target gene, is controlled cooperatively by MYB, C/EBPβ, and co-activator p300, and is down-regulated by C/EBPβ-inhibitory STLs, exemplifying that they target the activity of composite MYB-C/EBPβ-p300 transcriptional modules. Ectopic expression of GFI1, a zinc-finger protein that is required for the maintenance of hematopoietic stem and progenitor cells, partially abrogated STL-induced myelomonocytic differentiation, implicating GFI1 as a relevant target of C/EBPβ-inhibitory STLs. Overall, our data identify C/EBPβ as a pro-leukemogenic factor in AML and suggest that targeting of C/EBPβ may have therapeutic potential against AML. |
| اللغة: | English |
| تدمد: | 1476-5594 0950-9232 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::99594c1cb67990ef093aab785965f213Test http://europepmc.org/articles/PMC8298201Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....99594c1cb67990ef093aab785965f213 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765594 09509232 |
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