| Title | BCR-ABL suppresses C/EBPα expression through inhibitory action of hnRNP E2 |
|---|---|
| Publication Type | Articolo su Rivista peer-reviewed |
| Year of Publication | 2002 |
| Authors | Perrotti, D., Cesi Vincenzo, Trotta R., Guerzoni C., Santilli G., Campbell K., Iervolino A., Condorelli F., Gambacorti-Passerini C., Caligiuri M.A., and Calabretta B. |
| Journal | Nature Genetics |
| Volume | 30 |
| Pagination | 48-58 |
| ISSN | 10614036 |
| Keywords | animal cell, Animalia, Animals, Apoptosis, article, BCR ABL protein, bcr-abl, blast cell crisis, Blast Crisis, bone marrow cell, Carrier Proteins, CCAAT-Enhancer-Binding Protein-alpha, cell death, cell differentiation, Cells, Chronic myeloid leukemia, Cultured, DNA-Binding Proteins, Down-Regulation, Fusion proteins, gene expression regulation, Genetic, granulocyte colony stimulating factor receptor, Granulocyte Colony-Stimulating Factor, hematopoietic cell, Hematopoietic Stem Cells, Heterogeneous-Nuclear Ribonucleoproteins, Humans, K562 Cells, Leukemia, Leukemic, Messenger, Mice, Myeloid, Myeloid Cells, Neoplasm Proteins, nonhuman, Nucleic Acid, Oligodeoxyribonucleotides, oncoprotein, Philadelphia-Positive, Piperazines, priority journal, Protein Biosynthesis, protein expression, Protein Isoforms, protein protein interaction, Pyrimidines, receptor down regulation, Receptors, RNA, RNA-Binding Proteins, Sequence Alignment, sequence homology, stem cell, Transcription, Transcription Factors, Transfection, translation regulation, Tumor Stem Cells |
| Abstract | The arrest of differentiation is a feature of both chronic myelogenous leukemia cells in myeloid blast crisis and myeloid precursors that ectopically express the p210BCR-ABL oncoprotein; however, its underlying mechanisms remain poorly understood. Here we show that expression of BCR-ABL in myeloid precursor cells leads to transcriptional suppression of the granulocyte colony-stimulating factor receptor G-CSF-R (encoded by CSF3R), possibly through down-modulation of C/EBPα - the principal regulator of granulocytic differentiation. Expression of C/EBPα protein is barely detectable in primary marrow cells taken from individuals affected with chronic myeloid leukemia in blast crisis. In contrast, CEBPA RNA is clearly present. Ectopic expression of C/EBPα induces granulocytic differentiation of myeloid precursor cells expressing BCR-ABL. Expression of C/EBPα is suppressed at the translational level by interaction of the poly(rC)-binding protein hnRNP E2 with CEBPA mRNA, and ectopic expression of hnRNP E2 in myeloid precursor cells down-regulates both C/EBPα and G-CSF-R and leads to rapid cell death on treatment with G-CSF (encoded by CSF3). Our results indicate that BCR-ABL regulates the expression of C/EBPα by inducing hnRNP E2 - which inhibits the translation of CEBPA mRNA. |
| Notes | cited By 268 |
| URL | https://www.scopus.com/inward/record.uri?eid=2-s2.0-0036340784&doi=10.1038%2fng791&partnerID=40&md5=361c7bc4e9201bbe257b174dcb18a9a7 |
| DOI | 10.1038/ng791 |
| Citation Key | Perrotti200248 |
