HOX11 interacts with CTF1 and mediates hematopoietic precursor cell immortalization

HOX11 is a homeodomain-containing oncogenic transcription factor that immor talizes hematopoietic precursor cells. The mechanism by which HOX11 facilit ates this initial step of leukemogenesis is, however, not well understood. We have used a DNA binding site selection assay to investigate cooperative DNA binding by HOX11 with other transcription factors. A consensus sequence was derived and identified as the binding site for the CCAAT-box-binding t ranscription factors (CTF), HOX11 was shown to interact in vitro and in viv o with CTF1. Retrovirus-mediated transduction of an antisense CTF1 cDNA dra matically reduced the proliferative capacity of HOX11-immortalized hematopo ietic precursor cells. CTF1 is, therefore, the first HOX11 protein partner identified that plays an important role in hematopoietic precursor cell imm ortalization.