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HOX11 interacts with CTF1 and mediates hematopoietic precursor cell immortalization
1Department of Medicine, University of California, San Diego, La Jolla 92093-0671, USA.
Oncogene
|May 18, 1999
Summary
HOX11, a factor in leukemia, immortalizes precursor cells by binding DNA with CTF1. Inhibiting CTF1 reduced cell proliferation, identifying CTF1 as crucial for HOX11-driven immortalization.
Area of Science:
- Molecular Biology
- Oncology
- Hematopoiesis
Background:
- HOX11 is an oncogenic transcription factor implicated in immortalizing hematopoietic precursor cells.
- The precise mechanisms underlying HOX11's role in leukemogenesis remain incompletely understood.
Purpose of the Study:
- To investigate cooperative DNA binding mechanisms involving HOX11 and other transcription factors.
- To identify protein partners of HOX11 critical for hematopoietic precursor cell immortalization.
Main Methods:
- Utilized a DNA binding site selection assay to identify HOX11 binding sequences.
- Performed in vitro and in vivo interaction studies to confirm protein-protein binding.
- Employed retrovirus-mediated transduction of antisense CTF1 cDNA to assess functional impact.
Main Results:
- A consensus DNA binding sequence for HOX11 was identified as a binding site for CCAAT-box-binding transcription factors (CTF).
- HOX11 was demonstrated to interact with CTF1 both in vitro and in vivo.
- Suppression of CTF1 expression using antisense cDNA significantly impaired the proliferation of HOX11-immortalized cells.
Conclusions:
- CTF1 is the first identified HOX11 protein partner involved in hematopoietic precursor cell immortalization.
- The interaction between HOX11 and CTF1 is functionally significant for leukemogenesis.