The leukemia-associated protein Btg1 and the p53-regulated protein Btg2 interact with the homeoprotein Hoxb9 and enhance its transcriptional activation

BTG1 and BTG2 belong to a family of functionally related genes involved in the control of the cell cycle. As part of an ongoing attempt to understand their biological functions, we used a yeast two-hybrid screening to look fo r possible functional partners of Btg1 and Btg2. Here we report the physica l and functional association between these proteins and the homeodomain pro tein Hoxb9. We further show that Btg1 and Btg2 enhance Hoxb9-mediated trans cription in transfected cells, and we report the formation of a Hoxb9.Btg2 complex on a Hoxb9-responsive target, and the fact that this interaction fa cilitates the binding of Hoxb9 to DNA, The transcriptional activity of the Hoxb9.Btg complex is essentially dependent on the activation domain of Hoxb 9, located in the N-terminal portion of the protein, Our data indicate that Btg1 and Btg2 act as transcriptional cofactors of the Hoxb9 protein, and s uggest that this interaction may mediate their antiproliferative function.