This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Choi, J.
Right arrow Articles by Donehower, L. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Choi, J.
Right arrow Articles by Donehower, L. A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, February 2002, p. 1094-1105, Vol. 22, No. 4
0270-7306/01/$04.00+0     DOI: 10.1128/MCB.22.4.1094-1105.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Mice Deficient for the Wild-Type p53-Induced Phosphatase Gene (Wip1) Exhibit Defects in Reproductive Organs, Immune Function, and Cell Cycle Control

Jene Choi,1,2 Bonnie Nannenga,3 Oleg N. Demidov,4 Dmitry V. Bulavin,4 Austin Cooney,3 Cory Brayton,5 Yongxin Zhang,1 Innocent N. Mbawuike,1 Allan Bradley,6,7 Ettore Appella,4 and Lawrence A. Donehower1,3*

Department of Molecular Virology and Microbiology,1 Department of Molecular and Cellular Biology,3 Center for Comparative Medicine,5 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030,6 Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea,2 Laboratory of Cell Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892,4 The Sanger Centre, Wellcome Trust Genome Campus, Cambridgeshire CB10 1SA, United Kingdom7

Received 8 August 2001/ Returned for modification 3 October 2001/ Accepted 12 November 2001

The Wip1 gene is a serine/threonine phosphatase that is induced in a p53-dependent manner by DNA-damaging agents. We show here that Wip1 message is expressed in moderate levels in all organs, but is present at very high levels in the testes, particularly in the postmeiotic round spermatid compartment of the seminiferous tubules. We have confirmed that Wip1 mRNA is induced by ionizing radiation in mouse tissues in a p53-dependent manner. To further determine the normal biological function of Wip1 in mammalian organisms, we have generated Wip1-deficient mice. Wip1 null mice are viable but show a variety of postnatal abnormalities, including variable male runting, male reproductive organ atrophy, reduced male fertility, and reduced male longevity. Mice lacking Wip1 show increased susceptibility to pathogens and diminished T- and B-cell function. Fibroblasts derived from Wip1 null embryos have decreased proliferation rates and appear to be compromised in entering mitosis. The data are consistent with an important role for Wip1 in spermatogenesis, lymphoid cell function, and cell cycle regulation.

* Corresponding author. Mailing address: Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Phone: (713) 798-3594. Fax: (713) 798-3490. E-mail: larryd{at}bcm.tmc.edu.

Molecular and Cellular Biology, February 2002, p. 1094-1105, Vol. 22, No. 4
0022-538X/01/$04.00+0     DOI: 10.1128/MCB.22.4.1094-1105.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Zhang, X., Lin, L., Guo, H., Yang, J., Jones, S. N., Jochemsen, A., Lu, X. (2009). Phosphorylation and Degradation of MdmX Is Inhibited by Wip1 Phosphatase in the DNA Damage Response. Cancer Res. 69: 7960-7968 [Abstract] [Full Text]  
  • Xia, Y., Ongusaha, P., Lee, S. W., Liou, Y.-C. (2009). Loss of Wip1 Sensitizes Cells to Stress- and DNA Damage-induced Apoptosis. J. Biol. Chem. 284: 17428-17437 [Abstract] [Full Text]  
  • Han, H.-S., Yu, E., Song, J.-Y., Park, J.-Y., Jang, S. J., Choi, J. (2009). The Estrogen Receptor {alpha} Pathway Induces Oncogenic Wip1 Phosphatase Gene Expression. Mol Cancer Res 7: 713-723 [Abstract] [Full Text]  
  • Chuman, Y., Kurihashi, W., Mizukami, Y., Nashimoto, T., Yagi, H., Sakaguchi, K. (2009). PPM1D430, a Novel Alternative Splicing Variant of the Human PPM1D, can Dephosphorylate p53 and Exhibits Specific Tissue Expression. J Biochem 145: 1-12 [Abstract] [Full Text]  
  • Rossi, M., Demidov, O. N., Anderson, C. W., Appella, E., Mazur, S. J. (2008). Induction of PPM1D following DNA-damaging treatments through a conserved p53 response element coincides with a shift in the use of transcription initiation sites. Nucleic Acids Res 36: 7168-7180 [Abstract] [Full Text]  
  • Yoda, A., Toyoshima, K., Watanabe, Y., Onishi, N., Hazaka, Y., Tsukuda, Y., Tsukada, J., Kondo, T., Tanaka, Y., Minami, Y. (2008). Arsenic Trioxide Augments Chk2/p53-mediated Apoptosis by Inhibiting Oncogenic Wip1 Phosphatase. J. Biol. Chem. 283: 18969-18979 [Abstract] [Full Text]  
  • Yoda, A., Xu, X. Z., Onishi, N., Toyoshima, K., Fujimoto, H., Kato, N., Oishi, I., Kondo, T., Minami, Y. (2006). Intrinsic Kinase Activity and SQ/TQ Domain of Chk2 Kinase as Well as N-terminal Domain of Wip1 Phosphatase Are Required for Regulation of Chk2 by Wip1. J. Biol. Chem. 281: 24847-24862 [Abstract] [Full Text]  
  • Schito, M. L., Demidov, O. N., Saito, S., Ashwell, J. D., Appella, E. (2006). Wip1 Phosphatase-Deficient Mice Exhibit Defective T Cell Maturation Due To Sustained p53 Activation.. J. Immunol. 176: 4818-4825 [Abstract] [Full Text]  
  • Proia, D. A., Nannenga, B. W., Donehower, L. A., Weigel, N. L. (2006). Dual Roles for the Phosphatase PPM1D in Regulating Progesterone Receptor Function. J. Biol. Chem. 281: 7089-7101 [Abstract] [Full Text]  
  • Lu, X., Nannenga, B., Donehower, L. A. (2005). PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints. Genes Dev. 19: 1162-1174 [Abstract] [Full Text]  
  • Rosenwald, A., Chuang, E. Y., Davis, R. E., Wiestner, A., Alizadeh, A. A., Arthur, D. C., Mitchell, J. B., Marti, G. E., Fowler, D. H., Wilson, W. H., Staudt, L. M. (2004). Fludarabine treatment of patients with chronic lymphocytic leukemia induces a p53-dependent gene expression response. Blood 104: 1428-1434 [Abstract] [Full Text]  
  • Morin, C. I., Huot, J. (2004). Recent Advances in Stress Signaling in Cancer. Cancer Res. 64: 1893-1898 [Abstract] [Full Text]  
  • Saito-Ohara, F., Imoto, I., Inoue, J., Hosoi, H., Nakagawara, A., Sugimoto, T., Inazawa, J. (2003). PPM1D Is a Potential Target for 17q Gain in Neuroblastoma. Cancer Res. 63: 1876-1883 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»