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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Binding Sites
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Cell Survival / genetics
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Cell Transformation, Neoplastic / genetics*
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Chromosomal Proteins, Non-Histone*
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Consensus Sequence
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DNA / metabolism
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DNA, Antisense / pharmacology
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DNA, Complementary / genetics
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Fungal Proteins / physiology*
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Hematopoietic Stem Cells / cytology*
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Homeodomain Proteins / physiology*
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Humans
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Leukemia / genetics*
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Oncogene Proteins / physiology*
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Protein Binding
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Proto-Oncogene Proteins
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Regulatory Sequences, Nucleic Acid
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Saccharomyces cerevisiae Proteins*
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Sequence Alignment
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Transcription Factors / metabolism
Substances
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CHL1 protein, S cerevisiae
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Chromosomal Proteins, Non-Histone
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DNA, Antisense
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DNA, Complementary
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Fungal Proteins
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Homeodomain Proteins
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Oncogene Proteins
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Proto-Oncogene Proteins
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Saccharomyces cerevisiae Proteins
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Transcription Factors
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TLX1 protein, human
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DNA