Controlled stem cell amplification by HOXB4 depends on its unique proline-rich region near the N terminus.
Blood
; 129(3): 319-323, 2017 01 19.
Article
en En
| MEDLINE
| ID: mdl-27827825
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.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
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Células Madre Hematopoyéticas
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Leucemia
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Proteínas de Homeodominio
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Autorrenovación de las Células
Idioma:
En
Revista:
Blood
Año:
2017
Tipo del documento:
Article