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
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
PubMed ID: 9009195
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