Controlled stem cell amplification by HOXB4 depends on its unique proline-rich region near the N terminus

作者：Cusan Monica; Vegi Naidu M; Mulaw Medhanie A; Bamezai Shiva; Kaiser Lisa M; Deshpande Aniruddha J; Greif Philipp A; Quintanilla Fend Leticia; Goellner Stefanie; Mueller Tidow Carsten; Humphries Keith R; Armstrong Scott A; Hiddemann Wolfgang; Feuring Buske Michaela; Buske Christian^*

来源：Blood, 2017, 129(3): 319-323.

DOI：10.1182/blood-2016-04-706978

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-termrepopulating hematopoietic stem cells in a controlledway. Herewe showinmice 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 highermammals. 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.

• 出版日期2017-1-19