Wip1, a novel human protein phosphatase that is induced in response to ionizing radiation in a p53-dependent manner

• Michele Fiscella

  Advanced BioScience Laboratories–Basic Research Program, Molecular Oncology Section, Molecular Virology and Carcinogenesis Laboratory, Frederick, MD 21702; Laboratory of Cell Biology and Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, 37 Convent Drive, MSC 4255, Bethesda, MD 20892-4255; and Department of Microbiology and Immunology, and Kimmel Cancer Institute, Jefferson Medical College, Thomas Jefferson University,...

• HongLiang Zhang

  Advanced BioScience Laboratories–Basic Research Program, Molecular Oncology Section, Molecular Virology and Carcinogenesis Laboratory, Frederick, MD 21702; Laboratory of Cell Biology and Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, 37 Convent Drive, MSC 4255, Bethesda, MD 20892-4255; and Department of Microbiology and Immunology, and Kimmel Cancer Institute, Jefferson Medical College, Thomas Jefferson University,...

• Saijun Fan

  Advanced BioScience Laboratories–Basic Research Program, Molecular Oncology Section, Molecular Virology and Carcinogenesis Laboratory, Frederick, MD 21702; Laboratory of Cell Biology and Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, 37 Convent Drive, MSC 4255, Bethesda, MD 20892-4255; and Department of Microbiology and Immunology, and Kimmel Cancer Institute, Jefferson Medical College, Thomas Jefferson University,...

• Kazuyasu Sakaguchi

  Advanced BioScience Laboratories–Basic Research Program, Molecular Oncology Section, Molecular Virology and Carcinogenesis Laboratory, Frederick, MD 21702; Laboratory of Cell Biology and Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, 37 Convent Drive, MSC 4255, Bethesda, MD 20892-4255; and Department of Microbiology and Immunology, and Kimmel Cancer Institute, Jefferson Medical College, Thomas Jefferson University,...

• Songfa Shen

  Advanced BioScience Laboratories–Basic Research Program, Molecular Oncology Section, Molecular Virology and Carcinogenesis Laboratory, Frederick, MD 21702; Laboratory of Cell Biology and Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, 37 Convent Drive, MSC 4255, Bethesda, MD 20892-4255; and Department of Microbiology and Immunology, and Kimmel Cancer Institute, Jefferson Medical College, Thomas Jefferson University,...

• W. Edward Mercer

  Advanced BioScience Laboratories–Basic Research Program, Molecular Oncology Section, Molecular Virology and Carcinogenesis Laboratory, Frederick, MD 21702; Laboratory of Cell Biology and Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, 37 Convent Drive, MSC 4255, Bethesda, MD 20892-4255; and Department of Microbiology and Immunology, and Kimmel Cancer Institute, Jefferson Medical College, Thomas Jefferson University,...

• George F. Vande Woude

  Advanced BioScience Laboratories–Basic Research Program, Molecular Oncology Section, Molecular Virology and Carcinogenesis Laboratory, Frederick, MD 21702; Laboratory of Cell Biology and Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, 37 Convent Drive, MSC 4255, Bethesda, MD 20892-4255; and Department of Microbiology and Immunology, and Kimmel Cancer Institute, Jefferson Medical College, Thomas Jefferson University,...

• Patrick M. O’Connor

  Advanced BioScience Laboratories–Basic Research Program, Molecular Oncology Section, Molecular Virology and Carcinogenesis Laboratory, Frederick, MD 21702; Laboratory of Cell Biology and Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, 37 Convent Drive, MSC 4255, Bethesda, MD 20892-4255; and Department of Microbiology and Immunology, and Kimmel Cancer Institute, Jefferson Medical College, Thomas Jefferson University,...

• Ettore Appella

  Advanced BioScience Laboratories–Basic Research Program, Molecular Oncology Section, Molecular Virology and Carcinogenesis Laboratory, Frederick, MD 21702; Laboratory of Cell Biology and Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, 37 Convent Drive, MSC 4255, Bethesda, MD 20892-4255; and Department of Microbiology and Immunology, and Kimmel Cancer Institute, Jefferson Medical College, Thomas Jefferson University,...

抄録

Exposure of mammalian cells to ionizing radiation (IR) induces a complex array of cellular responses including cell cycle arrest and/or apoptosis. IR-induced G 1 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 both 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 gene, wip1. In vitro , recombinant Wip1 displayed characteristics of a type 2C phosphatase, including Mg 2+ 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.

収録刊行物

• Proceedings of the National Academy of Sciences

  Proceedings of the National Academy of Sciences 94 (12), 6048-6053, 1997-06-10

  Proceedings of the National Academy of Sciences

キーワード

• Multidisciplinary

詳細情報

• CRID: 1363951794599268864
• NII論文ID: 80009741416
• DOI: 10.1073/pnas.94.12.6048
• ISSN: 10916490
• ISSN: 00278424
• ISSN: http://id.crossref.org/issn/13460706
• Web Site: https://pnas.org/doi/pdf/10.1073/pnas.94.12.6048
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