3 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 reg ion of the t(10;14) chromosomal translocation recurring in T-cell acut e lymphoblastic leukemia. Here we demonstrate that the HOX-11 homeopro tein mediates transactivation of reporter genes through various promot ers in both mammalian and yeast cells. By deletion analysis, the trans activation domains of HOX-11 have been mapped to three amino acid stre tches in the homeoprotein, the glycine-proline-rich region at the amin o terminus, the homeodomain and the glutamine-rich region at the carbo xyl terminus. The three distinct functional domains of HOX-11 act in c oncert for optimal transactivation. In addition, the homeodomain of HO X-11 appears to be differentially utilized in a promoter-dependent man ner. Our data support the notion that the HOX-11 homeoprotein function s as an oncogenic transcription activator in leukemogenesis.