Controlled stem cell amplification by HOXB4 depends on its unique proline-rich region near the N terminus Journal Article
| Authors: | Cusan, M.; Vegi, N. M.; Mulaw, M. A.; Bamezai, S.; Kaiser, L. M.; Deshpande, A. J.; Greif, P. A.; Quintanilla-Fend, L.; Göllner, S.; Müller-Tidow, C.; Humphries, K. R.; Armstrong, S. A.; Hiddemann, W.; Feuring-Buske, M.; Buske, C. |
| Article Title: | Controlled stem cell amplification by HOXB4 depends on its unique proline-rich region near the N terminus |
| Abstract: | There is high interest in understanding the mechanisms that drive self-renewal of stem cells. HOXB4 is one of the few transcription factors that can amplify long-term repopulating hematopoietic stem cells in a controlled way. Here we show in mice that this characteristic of HOXB4 depends on a proline-rich sequence near the N terminus, which is unique among HOX genes and highly conserved in higher mammals. Deletion of this domain substantially enhanced the oncogenicity of HOXB4, inducing acute leukemia in mice. Conversely, insertion of the domain into Hoxa9 impaired leukemogenicity of this homeobox gene. These results indicate that proline-rich stretches attenuate the potential of stem cell active homeobox genes to acquire oncogenic properties. © 2017 by The American Society of Hematology. |
| Keywords: | leukemia; sequence analysis; genetics; mouse; animal; animals; mice; transcription factor; homeodomain proteins; physiology; transcription factors; hematopoietic stem cells; hematopoietic stem cell; homeodomain protein; acute disease; proline; sequence analysis, protein; carcinogen; carcinogens; cell self-renewal; cell self renewal; hoxb4 protein, mouse |
| Journal Title: | Blood |
| Volume: | 129 |
| Issue: | 3 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2017-01-19 |
| Start Page: | 319 |
| End Page: | 323 |
| Language: | English |
| DOI: | 10.1182/blood-2016-04-706978 |
| PUBMED: | 27827825 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 October 2017 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work