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. HOX11 is also oncogenic, having been isolated from a chromosomal breakpoint in human T-cell leukaemia. Transgenic mice that redirected HOX11 to the thymus demonstrated cell-cycle aberration and progression to malignancy. 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 regulate the cell cycle and control the activation of maturation-promoting factor in Xenopus oocytes. 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 by expression of 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. This interaction suggests a mechanism by which a homeobox can alter the cell cycle.
Mesh Terms:
Animals, Binding Sites, Cell Cycle, G2 Phase, Gamma Rays, Homeodomain Proteins, Humans, Jurkat Cells, Mice, Mitosis, Oncogene Proteins, Oocytes, Phosphoprotein Phosphatases, Protein Binding, Protein Phosphatase 1, Protein Phosphatase 2, Proto-Oncogene Proteins, Recombinant Fusion Proteins, T-Lymphocytes, Tumor Cells, Cultured, Xenopus, Xenopus Proteins
Nature
Date: Jan. 30, 1997
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