Three distinct domains in the HOX-11 homeobox oncoprotein are required for optimal transactivation.
HOX-11 (tcl-3) is a homeobox oncogene isolated from the breakpoint region of the t(10;14) chromosomal translocation recurring in T-cell acute lymphoblastic leukemia. Here we demonstrate that the HOX-11 homeoprotein mediates transactivation of reporter genes through various promoters in both mammalian and yeast cells. By deletion analysis, the transactivation domains of HOX-11 have been mapped to three amino acid stretches in the homeoprotein, the glycine-proline-rich region at the amino terminus, the homeodomain and the glutamine-rich region at the carboxyl terminus. The three distinct functional domains of HOX-11 act in concert for optimal transactivation. In addition, the homeodomain of HOX-11 appears to be differentially utilized in a promoter-dependent manner. Our data support the notion that the HOX-11 homeoprotein functions as an oncogenic transcription activator in leukemogenesis.
Zhang
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Department of Medicine, University of California, San Diego, La Jolla 92093-0671, USA.
Shen
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W
Ho
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AD
Lu
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M
D016475:3T3 Cells; D000818:Animals; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016297:Mutagenesis, Site-Directed; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D017384:Sequence Deletion; D015533:Transcriptional Activation
D018398:Homeodomain Proteins; D015513:Oncogene Proteins; C487378:Tlx1 protein, mouse