Hoxa9 Transduction Induces Hematopoietic Stem and Progenitor Cell Activity through Direct Down-Regulation of Geminin Protein

摘要: Hoxb4, a 3′-located Hox gene, enhances hematopoietic stem cell (HSC) activity, while subset of 5′-located genes is involved in hematopoiesis and leukemogenesis, some them are common translocation partners for Nucleoporin 98 (Nup98) patients with leukemia. Although these gene derivatives believed to act as transcription regulators, the molecular involvement leukemogenesis remains largely elusive. Since we previously showed that Hoxb4 forms complex Roc1-Ddb1-Cul4a ubiquitin ligase core component functions an E3 activator Geminin, here examined activities genes, Hoxa9 Hoxc13, Nup98-Hoxa9. formed similar induce ubiquitination but others did not. Retroviral transduction-mediated overexpression or siRNA-mediated knock-down respectively down-regulated up-regulated Geminin cells. And transduction-induced repopulating clonogenic were suppressed by supertransduction. These findings suggest differ from Hoxc13 Nup98-Hoxa9 their role hematopoiesis, induces activity HSCs progenitors at least part through direct down-regulation Geminin.