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.