HOX11 interacts with CTF1 and mediates hematopoietic precursor cell immortalization

• Published in: Oncogene Vol. 18; no. 13; pp. 2273 - 2279
• Main Authors: NAN ZHANG, WEIFANG SHEN, HAWLEY, R. G, MING LU
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 01.04.1999; Nature Publishing Group
• Subjects: Antisense DNA; Binding Sites; Biological and medical sciences; Cell immortalization; Cell physiology; Cell Survival - genetics; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cell Transformation, Neoplastic - genetics; Chromosomal Proteins, Non-Histone; Consensus Sequence; Conserved sequence; DNA - metabolism; DNA, Antisense - pharmacology; DNA, Complementary - genetics; DNA-binding protein; Fundamental and applied biological sciences. Psychology; Fungal Proteins - physiology; Hematopoietic Stem Cells - cytology; Hemopoiesis; Homeobox; Homeodomain Proteins - physiology; Humans; Immortalization; Leukemia - genetics; Leukemogenesis; Molecular and cellular biology; Nucleotide sequence; Oncogene Proteins - physiology; Protein Binding; Proto-Oncogene Proteins; Regulatory Sequences, Nucleic Acid; Saccharomyces cerevisiae Proteins; Sequence Alignment; Transcription factors; Transcription Factors - metabolism; Homeotic gene; Tumor progression; Hematopoietic cell; Molecular interaction; Binding site; Cell immortalization; Transcription factor
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1202545

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.