HOX11 interacts with CTF1 and mediates hematopoietic precursor cell immortalization.
HOX11 is a homeodomain-containing oncogenic transcription factor that immortalizes hematopoietic precursor cells. The mechanism by which HOX11 facilitates 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 transcription factors (CTF). HOX11 was shown to interact in vitro and in vivo with CTF1. Retrovirus-mediated transduction of an antisense CTF1 cDNA dramatically reduced the proliferative capacity of HOX11-immortalized hematopoietic precursor cells. CTF1 is, therefore, the first HOX11 protein partner identified that plays an important role in hematopoietic precursor cell immortalization.
D001665:Binding Sites; D002470:Cell Survival / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone; D016384:Consensus Sequence; D004247:DNA / Q000378:metabolism; D016373:DNA, Antisense / Q000494:pharmacology; D018076:DNA, Complementary / Q000235:genetics; D005656:Fungal Proteins / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D018398:Homeodomain Proteins / Q000502:physiology*; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D015513:Oncogene Proteins / Q000502:physiology*; D011485:Protein Binding; D011518:Proto-Oncogene Proteins; D012045:Regulatory Sequences, Nucleic Acid; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D014157:Transcription Factors / Q000378:metabolism