HOX11 interacts with protein phosphatases PP2A and PP1 and disrupts a G2/M cell-cycle checkpoint

Hox11 is an orphan homeobox gene that controls the genesis of the spleen(1). HOX11 is also oncogenic, having been isolated from a chromosomal breakpoint in human T-cell leukaemia(2-4). Transgenic mice that redirected HOX11 to the thymus demonstrated cell-cycle aberration and progression to malignancy(5). We observed that the protein HOX11 interacted with protein serine-threonine phosphatase 2A catalytic subunit (PP2AC), as well as protein phosphatase 1 (PP1C) in mammalian cells. Inhibition of PP2A can relate the cell cycle and control the activation of maturation-promoting factor in Xenopus oocytes(6). Microinjection of HOX11 into Xenopus oocytes arrested at the G2. phase of the cell cycle promoted progression to the M phase. G2 arrest can be induced by gamma-irradiation, but is eliminated bt expression oi HOX11 within a T-cell line. Thus HOX11 is a cellular oncogene that targets PP2A and PP1, both of which are targets for oncogenic viruses and chemical tumour promoters(7,8). This interaction suggests a mechanism by which a homeobox can alter the cell cycle.