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Wip1, a Novel Human Protein Phosphatase That Is Induced in Response to Ionizing Radiation in a P53-Dependent Manner

  1. Author:
    Fiscella, M.
    Zhang, H. L.
    Fan, S. J.
    Sakaguchi, K.
    Shen, S. F.
    Mercer, W. E.
    Vande Woude, G. F.
    Oconnor, P. M.
    Appella, E

  2. Author Address

    Appella E NCI CELL BIOL LAB DIV BASIC SCI NIH 37 CONVENT DR MSC 4255 BETHESDA, MD 20892 USA NCI CELL BIOL LAB DIV BASIC SCI NIH BETHESDA, MD 20892 USA ADV BIOSCI LABS BASIC RES PROGRAM MOL ONCOL SECT MOL VIROL & CARCINOGENESIS LAB FREDERICK, MD 21702 USA NCI MOL PHARMACOL LAB DIV BASIC SCI NIH BETHESDA, MD 20892 USA THOMAS JEFFERSON UNIV JEFFERSON MED COLL DEPT MICROBIOL & IMMUNOL PHILADELPHIA, PA 19107 USA THOMAS JEFFERSON UNIV JEFFERSON MED COLL KIMMEL CANC INST PHILADELPHIA, PA 19107 USA
    1. Year: 1997
  2. Journal: Proceedings of the National Academy of Sciences of the United States of America
    1. 94
    2. 12
    3. Pages: 6048-6053
  4. Type of Article: Article
  1. Abstract:

    Exposure of mammalian cells to ionizing radiation (IR) induces a complex array of cellular responses including cell cycle arrest and/or apoptosis. IR-induced GI arrest has been shown to depend on the presence of the tumor suppressor p53, which acts as a transcriptional activator of several genes, p53 also plays a role in the induction of apoptosis in response to DNA damage, and this pathway can be activated by bath transcription-dependent and -independent mechanisms, Here we report the identification of a novel transcript whose expression is induced in response to IR in a p53-dependent manner, and that shows homology to the type 2C protein phosphatases. We have named this novel gent, wip1. In vitro, recombinant Wip1 displayed characteristics of a type 2C phosphatase, including Mg2+ dependence and relative insensitivity to okadaic acid. Studies performed in several cell lines revealed that wip1 accumulation following IR correlates with the presence of wild-type p53, The accumulation of wip1 mRNA following IR was rapid and transient, and the protein was localized to the nucleus, Similar to waf1, ectopic expression of wip1 in human cells suppressed colony formation, These results suggest that Wip1 might contribute to growth inhibitory pathways activated in response to DNA damage in a p53-dependent manner. [References: 38]

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