Abstract
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.
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Acknowledgements
We thank Dr C Largman for critical reading of the manuscript and Dr R Tjian for providing the CTF1 cDNA. Supported by grants from NIH (DK49619), National Leukemia Research Association and National Cancer Institute of Canada (No. 8398).
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Zhang, N., Shen, W., Hawley, R. et al. HOX11 interacts with CTF1 and mediates hematopoietic precursor cell immortalization. Oncogene 18, 2273–2279 (1999). https://doi.org/10.1038/sj.onc.1202545
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DOI: https://doi.org/10.1038/sj.onc.1202545
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