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

Takumi Kawabe, Anthony J. Muslin and Stanley J. Korsmeyer
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Takumi Kawabe: Washington University School of Medicine
Anthony J. Muslin: Washington University School of Medicine
Stanley J. Korsmeyer: Washington University School of Medicine

Nature, 1997, vol. 385, issue 6615, 454-458

Abstract: Abstract Hoxl1 is an orphan homeobox gene that controls the genesis of the spleen1. HOX11 is also oncogenic, having been isolated from a chromosomal breakpoint in human T-cell leukaemia2–4. Transgenic mice that redirected HOX11 to the thymus demonstrated cell-cycle aberration and progression to malignancy5. 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 oocytes6. 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 λ-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 promoters7,8. This interaction suggests a mechanism by which a homeobox can alter the cell cycle.

Date: 1997
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DOI: 10.1038/385454a0

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